An open, randomized, parallel-group study was conducted to investigate whether asthmatic patients, considered adequately treated with a corticosteroid and/or short-acting beta 2-agonist via pressurized metered-dose inhaler (pMDI), could be transferred to a corresponding nominal dose of budesonide and/or terbutaline via Turbuhaler, an inspiratory flow-driven multidose dry powder inhaler (Astra Draco; Lund, Sweden), without a decrease in the effect of treatment. One thousand four patients (555 women; mean age, 44 years; mean peak expiratory flow [PEF], 102% predicted normal value) were randomized and treated with either pMDI (current therapy) or Turbuhaler for 52 weeks. The variables studied were asthma-related events, morning PEF, and inhaler-induced clinical symptoms. Asthma-related events were defined in two ways: (1) sum of health-care contacts plus doublings or additions of steroids, and (2) number of 2 consecutive days with PEF less than 80% of baseline. Baseline was obtained from a 2-week run-in period while receiving previous therapy. No statistically significant difference was found in asthma-related events according to definition 1. According to definition 2, there was a statistically significant difference between the groups in favor of Turbuhaler (p = 0.008). The mean number of events was 1.7 with Turbuhaler and 2.2 with pMDI. The mean number of weeks per patient with a PEF less than 90% of baseline was 4.5 with Turbuhaler compared with 6.0 with pMDI (p = 0.002). The sum of inhaler-induced symptoms after 1 year of use was statistically significantly lower with Turbuhaler (0.40) than with pMDI (0.75) (p = 0.0001). In conclusion, budesonide and terbutaline in Turbuhaler offered a superior alternative to corticosteroids and bronchodilators delivered by pMDIs in the maintenance treatment of asthma.
Thirty-one adult patients with asthma caused by house-dust mites (HDM) were included in this placebo-controlled, double-blind study to evaluate the efficacy and safety of specific immunotherapy (SIT) with biologically standardized extracts of HDM. The specific diagnosis was confirmed by skin prick tests, specific IgE, and bronchial provocation tests with HDM allergens. The patients were randomized to receive active treatment with extracts of either Dermatophagoides pteronyssinus (Dpt) or D. farinae (Dfa) (Alutard SQ, ALK, Denmark) or placebo injections. Twenty-three patients completed the study. After 1 year of treatment, we found a clinically important and significant reduction in both asthma medicine consumption (inhaled steroids 38% and beta 2-agonists 46%) and symptom score (57%) in the actively treated group, but not the placebo group. These findings were confirmed by a significant decrease in skin and bronchial sensitivity to HDM in the active group. Additionally, there was a significant difference in the patients' scores for effect in favor of the actively treated group. Total IgE and specific IgE to HDM showed no significant changes before and after treatment for either group. Spirometric lung-function measurements showed a significant increase in forced expiratory volume in 1 s (FEV1) from 85% before to 89% of predicted values after treatment for the actively treated group. Peak-flow measurements at home showed no significant changes during the study. It is concluded that allergen SIT is an effective treatment in adult patients suffering from asthma due to HDM.
The ß(2)-adrenergic receptor (ADRB2) is an important regulator of airway smooth muscle tone. We tested the hypothesis that three functional polymorphisms in the ADRB2 gene (Thr164Ile, Gly16Arg and Gln27Glu) are associated with reduced lung function, asthma or chronic obstructive pulmonary disease (COPD). We first genotyped 8,971 individuals from the Copenhagen City Heart Study for all three polymorphisms. To validate our findings, we genotyped an additional 53,777 individuals from the Copenhagen General Population Study for the Thr164Ile polymorphism. We identified 60,910 Thr164Ile noncarriers, 1,822 heterozygotes and 16 homozygotes. In the Copenhagen City Heart Study, the Thr164Ile genotype was associated with reduced forced expiratory volume in 1 s (FEV(1)) % predicted (trend p = 0.01) and FEV(1)/forced vital capacity (FVC) (p = 0.001): Thr164Ile heterozygotes had 3% and 2% reduced FEV(1) % pred and FEV(1)/FVC, respectively, compared with noncarriers. The odds ratio for COPD in Thr164Ile heterozygotes was 1.46 (95% CI 1.05-2.02). In the Copenhagen General Population Study, the Thr164 genotype associated with reduced FEV(1) % pred (p = 0.04) and FEV(1)/FVC (p
Nedocromil sodium is a pyranoquinoline dicarboxylic acid derivative, formulated in a metered-dose inhaler. Because nedocromil sodium has in vitro and in vivo anti-inflammatory properties, it was evaluated in a group of steroid-dependent patients with asthma to observe how well it might be tolerated and for evidence of any beneficial effects. In a double-blind, group-comparative study, 127 patients received nedocromil sodium and 61 received placebo, administered as two puffs of 2 mg, four times per day, for 12 weeks. Ten patients developed adverse reactions, seven receiving active drug and three patients receiving placebo. Two patients of each group withdrew because of worsening asthma. Despite selecting patients whose asthma was stable, when they were receiving established therapeutic regimens that included steroids and bronchodilators, it was found that diary-card symptom scores, morning and evening peak expiratory flow rate values, and inhaled beta-agonist usage all demonstrated slight but significant benefit with addition of nedocromil sodium. It is concluded that the inhaled, anti-inflammatory agent, nedocromil sodium, may be added to asthma-treatment regimens with the reasonable expectation of further modest symptomatic benefit.
Indoor climate of two new blocks of flats was investigated. The case building was built for people with respiratory diseases by following the instructions of the Finnish Classification of Indoor Climate, Construction and Finishing Materials, while the control building was built using conventional building technology. The main indoor air parameters (temperature, relative humidity and levels of CO, CO2, ammonia, total volatile organic compounds, total suspended particles, fungal spores, bacteria and cat, dog and house dust mite allergens) were measured in six apartments of both the buildings on five occasions during the 3-year occupancy. In addition, a questionnaire to evaluate symptoms of the occupants and their satisfaction with their home environment was conducted in connection with indoor air quality (IAQ) measurements. The levels of indoor air pollutants in the case building were, in general, lower than those in the control building. In addition, the asthmatic occupants informed that their symptoms had decreased during the occupancy in the case building. This case study showed that high IAQ is possible to reach by careful design, proper materials and equipment and on high-quality construction with reasonable additional costs. In addition, the study indicated that good IAQ can also be maintained during the occupancy, if sufficient information on factors affecting IAQ and guidance on proper use and care of equipment are available for occupants.
BACKGROUND: 5-Oxo-6,8,11,14-eicosatetraenoic acid (5-oxo-ETE) is an arachidonic acid metabolite with potent in vitro chemoattractant effects on eosinophils and neutrophils. It has also been shown to induce pulmonary eosinophilia in Brown Norway rats, but it is not known whether it is active in human beings in vivo. OBJECTIVE: To determine whether 5-oxo-ETE can induce cellular infiltration in patients with atopic asthma and nonatopic control subjects after intradermal administration. METHODS: 5-Oxo-ETE was administered intradermally to 11 patients with atopic asthma and 10 nonatopic control subjects. Skin biopsy specimens were taken 6 or 24 hours later and examined by immunocytochemistry for cells expressing specific markers for eosinophils (major basic protein), neutrophils (elastase), macrophages (CD68), lymphocytes (CD3), and mast cells (tryptase). RESULTS: 5-Oxo-ETE (1.5 and 5 microg) elicited the infiltration of both eosinophils and neutrophils into the skin in both control and atopic asthmatic subjects. Increased numbers of eosinophils were observed at 6 and 24 hours after injection, whereas significantly elevated neutrophil numbers were present only after 24 hours. Eosinophils were >3 times higher in patients with atopic asthma compared with control subjects after injection of the highest dose of 5-oxo-ETE. Macrophage numbers were also elevated, but only at the highest dose of 5-oxo-ETE. No effects were observed on the numbers of either lymphocytes or mast cells. CONCLUSIONS: 5-Oxo-ETE elicits the infiltration of eosinophils and neutrophils into the skin of human beings in vivo after intradermal administration. Asthmatic subjects are more responsive to this substance than nonallergic control subjects. These results suggest that 5-oxo-ETE may be an important mediator of inflammation.
A National Asthma Programme was undertaken in Finland from 1994 to 2004 to improve asthma care and prevent an increase in costs. The main goal was to lessen the burden of asthma to individuals and society.
The action programme focused on implementation of new knowledge, especially for primary care. The main premise underpinning the campaign was that asthma is an inflammatory disease and requires anti-inflammatory treatment from the outset. The key for implementation was an effective network of asthma-responsible professionals and development of a post hoc evaluation strategy. In 1997 Finnish pharmacies were included in the Pharmacy Programme and in 2002 a Childhood Asthma mini-Programme was launched.
The incidence of asthma is still increasing, but the burden of asthma has decreased considerably. The number of hospital days has fallen by 54% from 110 000 in 1993 to 51 000 in 2003, 69% in relation to the number of asthmatics (n = 135 363 and 207 757, respectively), with the trend still downwards. In 1993, 7212 patients of working age (9% of 80 133 asthmatics) received a disability pension from the Social Insurance Institution compared with 1741 in 2003 (1.5% of 116 067 asthmatics). The absolute decrease was 76%, and 83% in relation to the number of asthmatics. The increase in the cost of asthma (compensation for disability, drugs, hospital care, and outpatient doctor visits) ended: in 1993 the costs were 218 million euro which had fallen to 213.5 million euro in 2003. Costs per patient per year have decreased 36% (from 1611 euro to 1031 euro).
It is possible to reduce the morbidity of asthma and its impact on individuals as well as on society. Improvements would have taken place without the programme, but not of this magnitude.
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The prognosis of allergic rhinitis was studied in 154 children aged 3-17 years at diagnosis by means of a detailed questionnaire administered 8-11 years later. The symptoms had completely disappeared in only 15 (10%) patients. The conjunctival symptoms, however, had disappeared or were controlled successfully by topical drug therapy in almost all, and 77 (50%) were managing without medication for allergic rhinitis. Twenty-five (23%) of the 110 children with seasonal allergic rhinitis had a perennial disease at follow-up, in contrast to seven (16%) of 44 with perennial allergic rhinitis originally who had only seasonal symptoms at follow-up. Asthma or wheezing had developed in 29 cases (19%) and was more common (p less than 0.01) among those with perennial allergic rhinitis (15 of 44) than among those with seasonal allergic rhinitis (14 of 110). No significant association was found between age at onset of symptoms, family history of atopic disease or type of treatment for allergic rhinitis and allergic rhinitis still present at follow-up or development of asthma during the observation period.
The -112G>A polymorphism of the secretoglobin 3A2 (SCGB3A2) gene encoding uteroglobin-related protein 1 (UGRP1) increases risk for the development of Graves' disease in subsets of patients with elevated levels of immunoglobulin E.
The human secretoglobin 3A2 (SCGB3A2) gene encoding secretory uteroglobin-related protein 1 (UGRP1) resides on the chromosome region 5q31-33 that harbors a susceptibility locus to several autoimmune and inflammatory diseases, including asthma and Graves' disease (GD). Recently, association between the marker rs1368408 (-112G?>A), located in the promoter region of the SCGB3A2 gene, and susceptibility to GD was found in Chinese and UK Caucasians. The study aim was to evaluate whether this polymorphism confers GD susceptibility in a large population cohort comprising 1,474 Russian GD patients and 1,619 controls. The marker rs1368408 was studied using a TaqMan allele discrimination assay. Serum levels of UGRP1 and immunoglobulin E (IgE) were assessed using enzyme-linked immunosorbent assay (ELISA) analyses. Association between the allele A of SCGB3A2 and a higher risk of GD (odds ratio [OR] = 1.33, P = 2.9 × 10(-5)) was shown. Both affected and non-affected carriers of the higher risk genotype A/A had significantly decreased levels of serum UGRP1 compared to the subjects homozygous for G/G (93 ± 37 pg/ml vs. 132 ± 45 pg/ml, P = 0.0011 for GD patients; 77 ± 28 pg/ml vs. 119 ± 33 pg/ml, P = 0.0019 for controls). Serum IgE levels were significantly higher in non-affected subjects homozygous for A/A compared to control individuals homozygous for G/G (153 ± 46 IU/ml vs. 122 ± 40 IU/ml, P = 0.0095). Our data suggest that the carriage of the SCGB3A2 -112A/A variant increases the risk for GD in subsets of patients with elevated levels of IgE, a hallmark of allergic asthma. Therefore, the SCGB3A2 -112G?>A polymorphism may be considered as a likely marker linking susceptibility to allergy/asthma and GD on chromosome 5q31-33.