Christer Janson

Asthma, COPD and overlap syndrome : a longitudinal study in young European adults

We compared risk factors and clinical characteristics, 9-year lung function change and hospitalisation risk across subjects with the asthma–chronic obstructive pulmonary disease (COPD) overlap syndrome (ACOS), asthma or COPD alone, or none of these diseases. Participants in the European Community Respiratory Health Survey in 1991–1993 (aged 20–44u2005years) and 1999–2001 were included. Chronic airflow obstruction was defined as pre-bronchodilator forced expiratory volume in 1u2005s (FEV1)/forced vital capacity<lower limit of normal on both occasions. Based on their history of respiratory symptoms, spirometry and risk factors, subjects were classified as having asthma alone (n=941), COPD alone (n=166), ACOS (n=218) and none of these (n=5659). Subjects with ACOS shared risk factors and clinical characteristics with subjects with asthma alone, but they had an earlier age of asthma onset. FEV1 change in the ACOS group (−25.9u2005mL·year−1) was similar to that in the asthma group (−25.3u2005mL·year−1), and lower (p<0.001) than in the COPD group (−37.3u2005mL·year−1). ACOS was associated with the highest hospitalisation rate. Among young adults aged 20–44u2005years, ACOS seems to represent a form of severe asthma, characterised by more frequent hospitalisations, and to be the result of early-onset asthma that has progressed to fixed airflow obstruction. The asthma–COPD overlap syndrome in young adults is a form of early-onset severe asthma with recurrent exacerbations http://ow.ly/MHkss

Association of biomarkers of inflammation and cell adhesion with lung function in the elderly: a population-based study

BackgroundLow lung function is associated with increased morbidity and mortality. It is therefore of interest to identify biomarkers that are associated with impaired lung function. The aim of the study was to analyse associations of biomarkers and combinations of biomarkers with lung function in an elderly general population.MethodsLung function (FEV1 and FVC) and a panel of 15 inflammatory markers from blood samples were analysed in 888 subjects aged 70 years. Biomarkers included cytokines, chemokines, adhesion molecules, C-reactive protein (CRP) and leukocyte count.ResultsLeukocyte count and CRP were independently associated with FEV1 after adjustments for other inflammatory markers, sex, BMI, current smoking and pack-years of smoking. In a similar model, leukocyte count and vascular cell adhesion protein 1 (VCAM-1) were the biomarkers that were significantly associated with FVC. Subjects that had both leukocyte count and CRP in the lowest tertile had a FEV1 that was 9% of predicted higher than subjects with leukocyte count and CRP in the highest tertile (103±16 vs. 94±21% of predicted, p=0.0002) (mean±SD). A difference of 8% of predicted in FVC was found between subjects with leukocyte count and VCAM-1 in the lowest and highest tertiles, respectively (106±18 vs. 98±19% of predicted, p=0.002).ConclusionLeucocyte count, CRP and VCAM-1 were found to relate to poorer lung function. A dose related association was found for the combination leukocyte count and CRP towards FEV1 and leukocyte and VCAM-1 towards FVC. This indicates that combination of two biomarkers yielded more information than assessing them one by one when analysing the association between systemic inflammation and lung function.

Sublingual grass allergen specific immunotherapy: a retrospective study of clinical outcome and discontinuation

BackgroundSublingual immunotherapy (SLIT) is effective, tolerable, and convenient for many allergic patients. Still, real-world evidence is scarce and the aim of this study is to assess the patient reported outcome of treatment with SLIT against grass pollen allergy in a consecutive patient population.MethodsPatients (nu2009=u2009329) who were confirmed to be allergic to timothy grass and had been prescribed SLIT were consecutively enrolled in the study and completed a questionnaire online or in hard copy.Results207 (62.9%) patients responded to the questionnaire. The female/male ratio was 105/102 with a mean age of 39u2009±u200911xa0years (range 19–70xa0years). 113 (55%) patients reported they had completed the full 3-year treatment period, 49 (24%) were still on treatment, and 45 (22%) had discontinued treatment prematurely. Respondents who had completed the full treatment period reported that their allergy symptoms in the most recent grass pollen season had improved to a larger extent than subjects still on treatment or discontinuing the treatment prematurely. Improvement of asthma was twice as common among patients who completed compared to discontinued treatment (42 vs. 20%). Younger age (37u2009±u200912 vs. 41u2009±u200911xa0years, pu2009<u20090.001) and a higher prevalence of reported oral and/or gastrointestinal side effects (49 vs. 24%, pu2009=u20090.02) characterised the group that terminated SLIT. Forgetfulness was the most commonly reported specific reason.ConclusionTreatment perseverance resulted in improved patient reported outcome. Forgetfulness was the most frequently reported reason for discontinuing SLIT treatment against grass pollen allergy.

Exhaled nitric oxide in adolescence in relation to rhinitis symptoms 15 years later

Food hypersensitivity phenotypes among Swedish schoolchildren reporting partial avoidance of milkBackground: The insecticidal activity of plant lectins against a large array of insect species has been well documented. Insecticidal activities were found to be associated mostly with the two main groups of plant lectins: monocot mannose-binding and chitin binding lectin groups. Known as natural defense agents, plant lectins have been implicated as antibiosis factors against insects and considered as promising candidates for biological pesticides. Mistletoe (Viscum album) fruit lectin MChbL belongs to chitin-binding lectin group and is considered to expose toxic lesions on human. In vitro, plant lectins effect lymphocyte mitogenesis, aggregate immunoglobulins, induce histamine release from basophiles and mast cells. We have studied MChbL cytotoxicity towards human peripheral blood lymphocytes (PBL) in humans. Method: Human PBL culture was used to study MChbL cytotoxicity by mitogen stimulated MTT assay. PB from 15 volunteers were examined during this study and control group was compound from 12 healthy donors. The optical densities was measured on spectrophotometer Multiscan MCC at 570 nm wavelength. Results: Our study showed that any dose of mitogen ConA have stimulated the human PBL (1 lg/mL OD 0.198, 10 lg/mL OD 0.467, 100 lg/mL OD 0.344), whereas MChbL has inhibited the proliferation of PBL MChbL in both concentration (10 lg/ mL, 500 lg/mL) decreasing the amount of the cells and their viability. Particularly, this was obvious at higher concentration of MChbL 500 lg/mL applied (OD 0.60). Conclusion: MChbL expose cytotoxical effects to human peripheral blood lymphocytes (PBL), when administrated at high concentration 500 lg/mL. However, low concentrations of MChbL were less cytotoxic to PBL and exhibit similar results as ConA at the concentration of 1 lg/mL. Most likely, approaches to use MChbL as natural bio-pesticide must be considered at dose-dependent manner and administrated in the nontoxic range.

Clinical relevance of measuring IgE to cat allergen components

Background: Although pretreatment is not routinely used before immunotherapy, it has been shown to reduce the reactions in patients using rush, cluster and conventional schedules. Our aim is to determine the possible preventive effects of various premedication usage on systemic and local reactions during cluster immunotherapy. Method: One hundred and eighteen patients receiving a total of 137 cluster immunotherapy protocols to mites, pollens, bee and wasp venoms were recruited in the study. Patients were randomized into 5 different groups according to premedication status as shown here below: Group 1: daily levosetirizine, Group 2: levosetirizine only 2 h prior to injections, Group 3: daily montelukast, Group 4: combinations of montelukast and levosetirizine and, Group 5: no premedication Patients were followed during build up and maintenance phase of immunotherapy, systemic and local reactions were reported. Reactions are reported according to World Allergy Organization Subcutaneous Systemic Reaction Grading System. Results: Most of the patients were female (%64.2), the most frequent allergen was house dust mites (50.4%). Of 69.3% of patients took premedication and 19.7% of patients had reactions during the build up phase. Reactions were more frequent in patients who have pollen allergy and have received pollen immunotherapy [P = 0.034; OR = 2.65 CI:95%, 1.05–6.63)]. The total frequency of the hypersensitivity reaction was significantly higher in patients not receiving premedication [14 (14.7%) vs 13 (31.0%), P = 0.028 ]. However no difference was detected between groups taking various drugs for premedication. The patients in the premedication group significantly experienced less local reactions (P = 0.033) although no difference in the frequency of systemic reactions was seen between the groups. Conclusion: These preliminary results suggest that the reaction risk is increased in pollen immunotherapy and premedication does not seem to prevent the frequency or severity of systemic reactions although it decreases the frequency of local reactions. As the number of patients recruited in the study increases, the effect of premedication on reactions may be clearer.A three year follow-up of asthma, respiratory symptoms and self-reported allergy, among pilots and cabin attendants

A three year follow-up of asthma, respiratory symptoms and self-reported allergy, among pilots and cabin attendants

Background: Although pretreatment is not routinely used before immunotherapy, it has been shown to reduce the reactions in patients using rush, cluster and conventional schedules. Our aim is to determine the possible preventive effects of various premedication usage on systemic and local reactions during cluster immunotherapy. Method: One hundred and eighteen patients receiving a total of 137 cluster immunotherapy protocols to mites, pollens, bee and wasp venoms were recruited in the study. Patients were randomized into 5 different groups according to premedication status as shown here below: Group 1: daily levosetirizine, Group 2: levosetirizine only 2 h prior to injections, Group 3: daily montelukast, Group 4: combinations of montelukast and levosetirizine and, Group 5: no premedication Patients were followed during build up and maintenance phase of immunotherapy, systemic and local reactions were reported. Reactions are reported according to World Allergy Organization Subcutaneous Systemic Reaction Grading System. Results: Most of the patients were female (%64.2), the most frequent allergen was house dust mites (50.4%). Of 69.3% of patients took premedication and 19.7% of patients had reactions during the build up phase. Reactions were more frequent in patients who have pollen allergy and have received pollen immunotherapy [P = 0.034; OR = 2.65 CI:95%, 1.05–6.63)]. The total frequency of the hypersensitivity reaction was significantly higher in patients not receiving premedication [14 (14.7%) vs 13 (31.0%), P = 0.028 ]. However no difference was detected between groups taking various drugs for premedication. The patients in the premedication group significantly experienced less local reactions (P = 0.033) although no difference in the frequency of systemic reactions was seen between the groups. Conclusion: These preliminary results suggest that the reaction risk is increased in pollen immunotherapy and premedication does not seem to prevent the frequency or severity of systemic reactions although it decreases the frequency of local reactions. As the number of patients recruited in the study increases, the effect of premedication on reactions may be clearer.A three year follow-up of asthma, respiratory symptoms and self-reported allergy, among pilots and cabin attendants

The combination of elevated FeNO and blood eosinophils relates to poorer asthma control in young patients with allergic asthma

Background: Although pretreatment is not routinely used before immunotherapy, it has been shown to reduce the reactions in patients using rush, cluster and conventional schedules. Our aim is to determine the possible preventive effects of various premedication usage on systemic and local reactions during cluster immunotherapy. Method: One hundred and eighteen patients receiving a total of 137 cluster immunotherapy protocols to mites, pollens, bee and wasp venoms were recruited in the study. Patients were randomized into 5 different groups according to premedication status as shown here below: Group 1: daily levosetirizine, Group 2: levosetirizine only 2 h prior to injections, Group 3: daily montelukast, Group 4: combinations of montelukast and levosetirizine and, Group 5: no premedication Patients were followed during build up and maintenance phase of immunotherapy, systemic and local reactions were reported. Reactions are reported according to World Allergy Organization Subcutaneous Systemic Reaction Grading System. Results: Most of the patients were female (%64.2), the most frequent allergen was house dust mites (50.4%). Of 69.3% of patients took premedication and 19.7% of patients had reactions during the build up phase. Reactions were more frequent in patients who have pollen allergy and have received pollen immunotherapy [P = 0.034; OR = 2.65 CI:95%, 1.05–6.63)]. The total frequency of the hypersensitivity reaction was significantly higher in patients not receiving premedication [14 (14.7%) vs 13 (31.0%), P = 0.028 ]. However no difference was detected between groups taking various drugs for premedication. The patients in the premedication group significantly experienced less local reactions (P = 0.033) although no difference in the frequency of systemic reactions was seen between the groups. Conclusion: These preliminary results suggest that the reaction risk is increased in pollen immunotherapy and premedication does not seem to prevent the frequency or severity of systemic reactions although it decreases the frequency of local reactions. As the number of patients recruited in the study increases, the effect of premedication on reactions may be clearer.A three year follow-up of asthma, respiratory symptoms and self-reported allergy, among pilots and cabin attendants

Sensitisation to the cat allergen component Fel d 4 is independently related to the degree of inflammation in young asthmatics

Background: A body of evidence indicates that epigenetic modifications, including DNA methylation, play relevant roles in the differentiation and functions of immune cells. Therefore, these modifications have been increasingly implicated in the pathophysiology of allergic diseases. However, little is known about changes in DNA methylation during oral immunotherapy (OIT) in young children with food allergies. Here, we present genome-wide data of DNA methylation before and after OIT. Method: We gave rush OIT to two pediatric patients with egg allergy. Both the patients became tolerant and could consume eggs 1 year after the initiation of the therapy. CD14-positive monocytes and CD4-positive T cells were positively selected from peripheral blood mononuclear cells by magnetic bead-conjugated antibodies before and one year after starting OIT. Genomic DNA was purified from these cells and subjected to the Infinium Methylation Assay (Illumina). Results: A significant number of methylation-targeted CpG sites were found to be differentially methylated between the monocytes and T cells indicating that the cells represent different epigenetic profiles. DNA methylation profiles before and after starting OIT in the same type of cells were better correlated to each other than those between the two patients either before or after OIT. Gene ontology analysis of genes that displayed significant changes in methylation of promoter sequences in T cells showed that genes involved in the MAPK pathway were enriched the most. Conclusion: These results provide evidence that epigenetics plays a role in acquiring immune tolerance during OIT and can help further our understanding of the mechanisms involved in the immune tolerance of food allergy. 2 Grass pollen subcutaneous and sublingual immunotherapy inhibit allergen-induced nasal responses and local Th2 cytokines: a randomised controlled trialCharacterization of dose-FEV1 response of tralokinumab, an investigational anti-IL13 monoclonal antibody in patients with uncontrolled asthma : a population pharmacokinetic/pharmacodynamic modeling analysis

IgE sensitisation to food allergens is independently associated with exhaled nitric oxide and blood eosinophils in asthmatics - results from the MIDAS study

Background: It was reported in two studies that inhalation challenges with HDM aggravated skin lesions in patients with atopic dermatitis, especially in those with concomitant allergic asthma. The effect of HDM inhalation on aggravating skin responses in patients with hand eczema had never been investigated. Method: Of 18 patients with vesicular hand eczema and HDM allergy (positive SPT to D. pteronyssinus) were investigated in a randomised, double-blind, placebocontrolled, cross-over study. Increasing concentrations of standardised HDM (80, 400, 2000, 10 000 BU/ml) were inhaled for 1 min at intervals of 15 min. The FEV1 was measured immediately before and after each dose, after the last challenge every 10 min for 1 h, and thereafter every hour for 7 h. The placebo challenge procedure was the same as described for the active suspension. The time interval between HDM and placebo was 2-4 weeks. Early asthmatic reactions and late asthmatic reactions (LAR) were defined as a placebocorrected fall of 15% or more from baseline of FEV1. Hand eczema was scored according to the Dyshidrotic eczema Area and Severity Index (DASI) at baseline, 1, 6, 24 and 48 h. Total IgE was measured at the start of the first provocation day and serum eosinophils on both provocation days before the first challenge and 24 h later. Results: Significant increases in median DASI score and median DASI sub-scores were seen only after HDM provocation. After placebo provocation, no significant differences from baseline were seen. The median DASI increased significantly as compared with baseline at 6 and 48 h after HDM inhalation. This increase was significantly different between the provocations at 6 h. The median vesicles score increased significantly from baseline at 24 and 48 h. Patients with a placebo-corrected increase of vesicles at 24 and 48 h had significantly more often a LAR than those without an increase of vesicles. Patients with a placebo- corrected increase of the DASI at 24 h had as a group a higher mean total IgE level than those without an increase of the DASI. The increase in serum eosinophils 24 h after HDM provocation was not significantly different between the placebocorrected skin responders and non-skin responders. Conclusion: Hand eczema increased significantly more after HDM provocation than after placebo provocation. An increase of vesicles was preceded by a LAR. The group patients with an increase of hand eczema tended to have a higher mean total IgE level.