Optimal activation of T lymphocytes requires a costimulatory signal provided by the interaction of molecules on the surface of T cells with their ligands expressed on dendritic cells (DC). We investigated whether DC differentiated from monocytes from healthy and birch allergic asthmatic individuals and further maturated by stimulation with cat and birch allergens and LPS differ in their phenotypic receptor expression. Similar expression of DC surface markers, including HLA-DR, CD80, CD86, CD83, CD1a and CD11c, was detected in monocyte-derived DC from allergic and healthy individuals. Cells from healthy donors stimulated either antigen showed a similar activation of the CD80 and double CD80/CD86 costimulatory molecules when compared with non-stimulated cells. In the case of cells from allergic individuals, birch allergen was unable to produce the same increased expression of CD80 alone or in combination with CD80/CD86, in comparison with cells stimulated with cat and LPS. Levels of IL-6, IL-8, IL-10, MCP-1/MCAF and MIP-1β were similar in the supernatant of non-stimulated DC from both groups of subjects. By contrast, the spontaneous secretion of IL-12p70 and TNF-α was higher in the supernatant of DC from healthy subjects when compared with that from allergic individuals. Stimulation with birch and LPS resulted in an increased secretion of IL-12p70 in samples from healthy when compared with that in allergic individuals. The results suggest an impaired specific maturation of DC from birch allergic individuals in association with birch-specific immune responses. Lower secretion of IL-12p70 from birch-stimulated DC from allergic individuals suggests that not only maturation, but also the specific Th1 function of these cells seems to be affected in those individuals.

This unique manual provides comprehensive, practical, and easily accessible guidelines on the key points of asthma management in both adults and children. The updated 2nd edition incorporates the most recent national and international guidelines for the care of asthmatic patients, with vital information on how to address clinical issues while emphasizing essential basic science in diagnosing, managing, and treating asthma.

Background: Pollen immunotherapy is effective in hay fever and asthma in children, although there are few studies on the long-term benefit.

Methods: We conducted a longitudinal follow up for 11 years of specific immunotherapy (SIT) for birch and or grass pollen allergy in children (n=28) who took part in the preventive allergic treatment (PAT) study. Bronchial hyperresponsiveness (BHR.) to methacholine, conjunctival provocation tests (CPT), and the skin sensitivity to common allergens-(SPT) were done. A matched group of patients who had not received immunotherapy served as controls.

Results: Eight years after of discontinuation of IT, 11 children with and 11 children without IT could be investigated. In the SIT group 2 had asthma compared to 7 in the control group. The skin and conjunctival sensitivity in the SIT group decreased more (n.s.). Birch pollen counts were measured dming the pollen seasons in every year from 1992 to 1995 and in the year 1997. The years 1993 and 1995 had high levels of birch pollen counts compared to the other years.

When all the children were considered, scores for asthma symptoms and BHR was higher in these years.

PEF variation decreased with age in both groups.

Conclusions: SIT for hay fever for three years induced a clinical remission 8 years after discontinuation of immunotherapy accompanied by a reduction in the degree of BHR, conjunctival sensitivity, number of allergen sensitizatlons, and occurrence of asthma symptoms.

Background: Exposure to indoor allergens play a major role for development of sensitization and induction of allergic inflammation, bronchial hyperreactivity and symptoms in sensitized individual.

Objective: fu this study, we investigated the individual exposure levels of cat allergen, Fel d1, among asthmatic schoolchildren sensitized to cats. We studied the exposure relationship with symptoms, medication, lung functions, bronchial hyperreactivity (BHR) and mediators of allergic inflallrmation.

Methods: Ten school children with known allergy to cats were selected from 5 schools in Linköping, Sweden. All children had positive skin test to cats. We collected dust samples from homes and schools. All children carried a portable air-sampler in the schools during the period of 4-6 weeks. Air was also sampled fi·om the bedroom. The children performed lung function (PEF) twice daily using a digital Peak flow meter. They maintain symptom and medication chart once in a week. We performed methacholine bronchial provocation test (PD₂₀) and analyzed mediators of allergic inflammation (s-ECP, EPX and MPO) iu blood and urine at the beginning and at the end of the study period. Dust and air samples were analyzed for major cat allergen (Fel d1) using ELISA.

Results: Exposure levels of cat allergen varied from 0,5 µg/g to 751 µg/g dust in homes (median, 36 µg/g) and from 17 µg/g to 378 µg/g in schools (median, 137 µg/g). Airborne allergen levels varied from 13 to 2184 pg/m³ (median, 43 pg/m³) in the homes and 68 to 7718 pg/m³ (median 352 pg/m³) in the schools. The mediators of allergic inflammation ranged from 4 to 57 µg/L for ECP, from 12 to 73 µg/L for EPX and from 148 to 581 µg/L for MPO. All children had bronchial hyperreactivity and all but one child used asthma/allergy medicine during the entire study period. A significant relationship (p<0.05) was found between the peak allergen exposure and symptoms, airborne allergens and BHR of the children.

Conclusions: Our study suggests, that school is an important source of cat allergen exposure, that cat sensitized asthmatic children inhale a substantial amount of cat allergen in the schools, that despite treatment of asthma including regular use of inhaled corticosteroids, 8 pg to 2336 pg of cat allergen inhaled per minute is sufficient enough to maintain a continuous airway hyper-responsiveness among this group of children.

Patients with mild intermittent asthma sometimes show signs of inflammation, and guidelines suggesting bronchodilator therapy alone as needed may be questioned. The current study compared as-needed use of a rapid-acting β2-agonist with as-needed use of a β2-agonist and corticosterold combination as the only medication in asthma patients with intermittent symptoms. A total of 92 nonsmoking asthma patients (of 187 screened) using only an inhaled β2-agonist as needed (28 males, 64 females, mean age 37 yrs, mean forced expiratory volume in one second (FEV1) 101% predicted, mean reversibility 6.5% pred and fractional exhaled nitric oxide (FeNO) ≥20 parts per billion (ppb)) were randomised to treatment with formoterol (Oxis® Turbuhaler®) 4.5 μg as needed (n=47) or budesonide/formoterol (Symbicort® Turbuhaler®) 160/4.5 pg as needed (n=45) in a double-blind, parallel-group 24-week study. The primary variable of efficacy was change in FeNO. Baseline FeNO was 60 ppb and 59 ppb in the budesonide/formoterol and formoterol groups, respectively. Mean reductions in FeNO in the budesonide/formoterol and formoterol groups were 18.2 ppb and 2.8 ppb, respectively (95% confidence interval (CI) 7.5-23.5 ppb). The reduction in the budesonide/formoterol group occurred during the first 4 weeks of treatment and remained at this low level. Mean FEV1 increased by 1.8% pred normal value in the budesonide/formoterol group and decreased by 0.9% pred normal value in the formoterol group (95% Cl -4.7 - -0.7). In the budesonide/formoterol group, use of ≥4 inhalations-day-1 of study medication was seen on 21 treatment days compared with 74 in the formoterol group. In conclusion, as-needed use of an inhaled corticosteroid together with a rapid-acting bronchodilator may be more beneficial than a β2-agonist alone in patients with intermittent asthma and signs of airway inflammation. The long-term benefits are unknown. Copyright © ERS Journals Ltd 2006.

Background: The inflammatory mechanisms of hypertonic saline-induced bronchoconstriction are not well understood. Methods: Seventeen asthmatics with (n = 11) and without bronchial hyperresponsiveness (BHR) (n = 6) and 18 randomly selected nonatopic nonasthmatic controls without BHR were evaluated by urine samples collected before and 1 h after hypertonic saline provocation test. Histamine, 11β-PGF2α, and LTE4 were analysed by enzyme immunoassay (EIA) and eosinophil protein X (EPX) by radioimmunoassay (RIA). Results: The levels of leukotriene E4 (LTE4) increased significantly after the challenge tests, both in the asthmatics (median: 354 pg/mg pre-challenge vs. 628 pg/mg post-challenge, P = 0.05) and in the controls (median: 294 pg/mg pre-challenge vs. 460 pg/mg post-challenge, P < 0.01). The levels of histamine also increased significantly in the latter (median: 299 μmol/mg pre-challenge vs. 569 μmol/mg post-challenge, P = 0.03). However, the levels of 11β-PGF2α and EPX did not change significantly after the challenge tests either in the asthmatics or in the controls. Conclusions: The inhalation of hypertonic saline increased urinary excretion of LTE4 both in the asthmatics and in the controls. The slight increase of leukotrienes was enough to induce airway obstruction in some of the asthmatics, because of the hyperresponsiveness in their airways.

Hypertonic saline provocation tests have been validated to be useful in the International Study of Asthma and Allergies in Childhood, but the inflammatory mechanisms of hypertonic saline-induced bronchial hyperresponsiveness (BHR) have not been well understood in asthmatic children. Of the 127 children who participated in hypertonic saline provocation tests, all asthmatics with (n = 13) and without BHR (n = 7) as well as all healthy controls without BHR (n = 37) were evaluated with urine samples collected before and one hour after the provocation test. Paired samples were analyzed in 11 asthmatics with and 6 asthmatics without BHR and 18 healthy controls. Urinary histamine, 11ß-PGF_2α and LTE₄ were analyzed by EIA and urinary EPX by RIA. The levels of LTE₄ increased after the challenge tests, both in the asthmatics (median value: 354.2 pg/mg pre-challenge vs. 628.3 pg/mg post-challenge, p = 0.05) and in the healthy controls (median value: 294.4 pg/mg pre-challenge vs. 460.0 pg/mg post-challenge, p = 0.008). The levels of histamine also increased in the latter (median value: 299.3 µmol/rug pro-challenge vs. 568.8 µmol/mg post-challenge, p = 0.03). However, the levels of 11ß-PGF_2α and EPX were similar before and after the challenge tests both in the asthmatics and in the healthy controls. The inhalation of hypertonic saline induced the secretion of LTE₄ and histamine even in healthy children, but the bronchoconstriction did not seem to be induced by the analyzed inflammatory mediators, such as LTE₄, 11ß-PGF_2α, histamine and EPX.

Hepatocyte growth factor (HGF) is a protein produced by mesenchymal cells in many organs, which can stimulate epithelial growth. An enhanced production and concentration of HGF is observed after injuries. The lung is one of the major sources of HGF. By cooling exhaled air, a condensate is formed containing molecules from bronchi and alveoli. In order to investigate HGF concentration and time course in pneumonia, paired serum and exhaled breath condensate was collected from 10 patients with pneumonia, 10 patients with non-respiratory infections and 11 healthy controls. The concentration of HGF was measured by an immunoassay kit. In the acute phase HGF-levels in breath condensate and serum were significantly higher in the patients with pneumonia compared to the control groups. Similar concentrations in breath condensate were seen in healthy controls and in patients with non-respiratory infections. In the patients with pneumonia a decrease in serum HGF was seen already after 4–7 days while HGF values in breath condensate remained elevated even after 4–6 weeks. These results might imply local production of HGF in the lungs and a long repair and healing process after pneumonia.

Both asthma and obesity have become more common in affluent societies during the recent decades and several studies have shown a correlation between the presence of asthma and obesity. In order to further study this association we have investigated a population from a community in southern Sweden, where almost all inhabitants had their body indices measured as part of a study on diabetes at a primary care centre. An asthma unit working with a structured care programme for asthma was available. This organisation enabled us to study whether body mass index and waist circumference was associated with having or developing asthma. There was a significant association between both overweight, increased waist circumference and asthma, P

Background: Childhood asthma has risen dramatically not only in the western societies and now forms a major and still increasing public health problem. The aims of this study were to follow up at the age of ten the patterns of asthma symptoms and associations among children with a clinically diagnosed asthma in a sizeable urban-rural community and to in compare them with demographic controls using a standardised questionnaire. Methods: In a defined region in Sweden with a population of about 150 000 inhabitants, all children (n = 2 104) born in 1990 were recorded. At the age of seven all primary care and hospital records of the 1 752 children still living in the community were examined, and a group of children (n = 191) was defined with a well-documented and medically confirmed asthma diagnosis. At the age of ten, 86 % of these cases (n = 158) and controls (n = 171) completed an ISAAC questionnaire concerning asthma history, symptoms and related conditions. Results: Different types of asthma symptoms were highly and significantly over-represented in the cases. Reported asthma heredity was significantly higher among the cases. No significant difference in reported allergic rhinitis or eczema as a child was found between cases and controls. No significant difference concerning social factors or environmental exposure was found between case and controls. Among the control group 4.7 % of the parents reported that their child actually had asthma. These are likely to be new asthma cases between the age of seven and ten and give an estimated asthma prevalence rate at the age of ten of 15.1 % in the studied cohort. Conclusion: A combination of medical verified asthma diagnosis through medical records and the use of self-reported symptom through the ISAAC questionnaire seem to be valid and reliable measures to follow-up childhood asthma in the local community. The asthma prevalence at the age of ten in the studied birth cohort is considerably higher than previous reports for Sweden. Both the high prevalence figure and allowing the three-year lag phase for further settling of events in the community point at the complementary roles of both hospital and primary care in the comprehensive coverage and control of childhood asthma in the community. © 2005 Roel et al, licensee BioMed Central Ltd.

Background: Eosinophilic inflammation of the airways is a key characteristic of asthma. A defect in eosinophil apoptosis might contribute to the chronic tissue eosinophilia associated with asthma. Objective: Our purpose was to examine whether the occurrence of apoptotic eosinophils in induced sputum from asthmatic patients correlate with interleukin (IL)-5 and eotaxin. Methods: Thirty stable and 30 exacerbated asthmatic patients were recruited. Twenty healthy subjects were enrolled as a control group. Induced sputum was obtained from asthmatic patients and from control subjects. The number of apoptotic eosinophils in sputum was assessed by flow cytometry. In sputum supernatant, eosinophil cationic protein (ECP) was measured by sensitive radioimmunoassay, and IL-5 and eotaxin by sandwich enzyme linked immunosorbant assay. Results: Levels of eosinophils, apoptotic eosinophils, IL-5, ECP and eotaxin from asthmatic patients were higher than those from healthy subjects. Thirty exacerbated asthmatics showed higher proportions of eosinophils (median 29.3%, range 13.4%-40.9%), more detectable levels of IL-5 (50.44, 32.99-67.01 pg/ml) and eotaxin (644.6, 197.4-937.7 pg/ml) in their sputum than the patients with stable asthma (P < 0.05). There were significant inverse correlations between the levels of sputum IL-5 and the proportion of sputum eosinophil apoptosis in patients with exacerbated and stable asthma (r = - 0.85 and -0.79, P < 0.01 and P < 0.05, respectively). Also inverse correlations were found between the levels of eotaxin and the proportion of sputum eosinophil apoptosis in exacerbated (r = - 0.85, P < 0.01), or stable asthma (r = - 0.69, P < 0.05). Additional positive corrlations between the levels of sputum IL-5 and eotaxin in either exacerbatated (r = 0.93, P < 0.01) or stable asthma (r = 0.82, P < 0.05) were observed. Conclusions: Apoptosis of eosinophils might be suppressed by proinflammatory cytokines and chemokines such as IL-5 and eotaxin leading to their accumulation in the lung. Stimulation of eosinophils in airway with IL-5 and eotaxin may play a crucial role in allergic inflammation. © 2007 Elsevier Ltd. All rights reserved.

Asthma is a chronic inflammatory disorder of the airways that has a considerable socioeconomic impact. Asthma management guidelines have been introduced to help provide better long-term control of asthma. Although recommended guidelines may increase the direct medication costs, the overall direct costs of asthma may be reduced due to fewer exacerbations. In addition, indirect costs due to lost productivity and mortality are reduced and patients have an improved quality of life. Inhaled corticosteroids are first-line therapy in the treatment of persistent asthma. Against this background, we have assessed the cost-effectiveness of Symbicort(R) (budesonide and formoterol in a single inhaler), a treatment that provides better control of asthma compared with budesonide alone. While the prescribing costs of Symbicort(R) were found to be higher than for budesonide alone, these were partially offset by reduced costs due to fewer asthma exacerbations and a reduced need for other medications. Combined long-term therapy with budesonide and formoterol also improves patient quality of life compared with budesonide alone. Two other factors associated with asthma treatment success and cost-effectiveness are patient/physician education and good patient adherence to prescribed therapy. The introduction of a single inhaler that is easy to use in simple treatment regimens may improve patient adherence to prescribed medication, thus resulting in improved asthma control and fewer exacerbations. Treatment with Symbicort(R) is more cost-effective than treatment with budesonide alone.