Biomedical subjects

T Haahtela

Publications and source records attributed to T Haahtela.

At least 37 records · Page 2Linked to original sources

PubMed2004

Asthma and atopy - the price of affluence?

Irrespective of improved knowledge of many aspects of atopic diseases, the unfavorable trends in their prevalence particularly among children could not have been reversed. A growing body of evidence suggests that something may lack from our societal affluence that has the capacity to provide protection against the development of atopic diseases. Much attention during the last years has been devoted to the hygiene hypothesis. This review outlines the impact of environment and lifestyle, particularly from the perspective of the East-West gradient, on the development of atopic diseases, with a special emphasis on the hygiene hypothesis in its broadest sense.

Asthma↗

PubMed2004

Induced sputum in children with newly diagnosed mild asthma: the effect of 6 months of treatment with budesonide or disodium cromoglycate.

BACKGROUND: There are few controlled studies on the effects of anti-inflammatory treatment on airway inflammation in newly diagnosed childhood asthma. METHODS: Sixty children with newly diagnosed mild persistent asthma, 5-10 years of age, and 17 healthy control subjects were studied. Asthmatic children were randomized into an open study with two treatment groups: (1) budesonide 400 microg twice daily for 1 month, 200 microg twice daily for 5 months and (2) disodium cromoglycate (DSCG) 10 mg three-times daily for 6 months. All exacerbations were treated with budesonide 400 microg twice daily for 2 weeks. Symptoms and lung function were recorded throughout the study. RESULTS: Sputum induction was safe and the overall success rate was 71%. This improved with age and decreased after treatment. At baseline, the asthmatic children had more eosinophils in blood (0.26 vs 0.18 x 10(9)/l, P = 0.03) and sputum (1.1 vs 0.0 %, P = 0.0001) than the control subjects. The numbers of sputum eosinophils correlated with bronchial responsiveness (R = -0.58, P = 0.0002). Eosinophils were higher in children with atopic asthma than with nonatopic asthma (P < 0.0001), and in children with a history wheezing than in children without wheezing (P = 0.02). Six months of budesonide treatment, but not of DSCG, improved lung function (P = 0.007), decreased symptoms (P = 0.007) and sputum eosinophils (P = 0.003). The effects of budesonide were pronounced in children with intense sputum eosinophilia (>3%). CONCLUSION: Sputum eosinophilia is present in children with newly diagnosed mild persistent asthma. Treatment with inhaled budesonide, but not with DSCG, decreases sputum eosinophils along with clinical and functional improvement.

Asthma↗

PubMed2003

Smoking and atopy as determinants of sputum eosinophilia and bronchial hyper-responsiveness in adults with normal lung function.

Data concerning the determinants of sputum eosinophilia and bronchial hyper-responsiveness (BHR) in large cohorts of individuals with normal lung function are limited. Here, we assessed the occurrence of sputum eosinophilia and BHR and identified the risk factors for these variables in two populations living in North Karelia, Finland, and in Pitkäranta, the Republic of Karelia, Russia. These areas are geographically adjacent, but differ, however, fundamentally in major cultural, socioeconomical and lifestyle aspects. The study population comprised 790 Finns and 387 Russian, aged 25-54 years, who were randomly enrolled from the population registers. A methacholine challenge test to measure BHR was successfully performed in 581 (74%) Finns and 307 (79%) Russians with virtually normal lung function (FEV1 > 70% of predicted). Of these, induced sputum samples were obtained from 41% of the Finns and from 67% of the Russians. The proportion of current smokers was 27% among the former and 42% among the latter. Sputum eosinophilia was assessed using a semi-quantitative method, and total concentrations of sputum eosinophilic cationic protein (ECP) and myeloperoxidase (MPO) were measured using an immunoassay. Risk factors for BHR and sputum eosinophilia were identified with a regression analysis. The prevalence of sputum eosinophilia was 22% among the Finns and 19% among the Russians, and the respective figures for BHR were 14% and 13%. The median ECP concentration in sputum was significantly higher among the Russians as compared with the Finns (P<0.001), whereas for MPO, the difference did not achieve significance. Current smoking was significantly associated with both sputum eosinophilia and BHR in Russia (OR 3.1, 95% CI 1.2-7.6 for sputum eosinophilia, 2.8, 1.3-6.1 for BHR) and with BHR in Finland (2.1, 1.3-3.7). Atopy showed a tendency to be another risk factor for BHR in Finland (1.6, 0.98-2.6). In conclusion, sputum eosinophilia and BHR occurred commonly among the Finns and the Russians with normal lung function. Current smoking was significantly associated with BHR in both countries and additionally with sputum eosinophilia in Russia. Atopy was identified as a risk factor, albeit of borderline significance, for BHR in Finland only, suggesting that there may be differences in the aetiology and nature of BHR between the two countries.

Adult↗

PubMed2003

Intranasal exposure to a damp building mould, Stachybotrys chartarum, induces lung inflammation in mice by satratoxin-independent mechanisms.

BACKGROUND: Stachybotrys chartarum is a damp building mould and a potent toxin producer that has been related to serious cases of respiratory health problems. However, the direct link between exposure and health symptoms has not been established. OBJECTIVE: To examine the mechanism by which exposure to spores of satratoxin producing and non-producing S. chartarum strains induce inflammatory responses in murine lungs. METHODS: BALB/c mice were intranasally exposed for 3 weeks to spores of a satratoxin-producing and a non-producing S. chartarum strain. Inflammatory cell infiltration was characterized from bronchoalveolar lavage (BAL) fluid. Cytokine and chemokine mRNA expression in lung tissue was measured with real-time PCR. Bronchial responsiveness to methacholine (MCh) was determined by whole-body plethysmography and serum antibody levels by ELISA. RESULTS: A dose-dependent increase in monocytes, neutrophils and lymphocytes was observed in BAL fluid after intranasal (i.n.) instillation of S. chartarum spores. There was no difference in the BAL between exposure to the satratoxin-producing and the non-producing strains. Infiltration of inflammatory cells was associated with an induction of pro-inflammatory cytokine (IL-1beta, IL-6 and TNF-alpha) and chemokine (CCL3/MIP-1alpha, CCL4/MIP-1beta and CCL2/MCP-1) mRNA levels in the lungs. Interestingly, CXCL5/LIX was the only chemokine that showed significantly higher mRNA levels after exposure to the satratoxin-producing strain compared with the non-producing strain. MCh-induced bronchial responsiveness was not altered significantly after mould instillation. Moreover, no significant increase in total or specific IgE, IgG2a and IgG1 antibody levels were found after S. chartarum exposure. CONCLUSION: These results indicate that lung inflammation induced by i.n. instillations of S. chartarum spores is regulated by the induction of pro-inflammatory cytokines and leucocyte-attracting chemokines. The data also imply that S. chartarum-derived components, other than satratoxins, are mediating the development of this inflammatory response.

Administration, Intranasal↗

PubMed2003

Exhaled nitric oxide rather than lung function distinguishes preschool children with probable asthma.

BACKGROUND: Respiratory function and airway inflammation can be evaluated in preschool children with special techniques, but their relative power in identifying young children with asthma has not been studied. This study was undertaken to compare the value of exhaled nitric oxide (FE(NO)), baseline lung function, and bronchodilator responsiveness in identifying children with newly detected probable asthma. METHODS: Ninety six preschool children (age 3.8-7.5 years) with asthmatic symptoms or history and 62 age matched healthy non-atopic controls were studied. FE(NO) was measured with the standard online single exhalation technique, and baseline lung function and bronchodilator responsiveness were measured using impulse oscillometry (IOS). RESULTS: Children with probable asthma (n=21), characterised by recent recurrent wheeze, had a significantly higher mean (SE) concentration of FE(NO) than controls (22.1 (3.4) ppb v 5.3 (0.4) ppb; mean difference 16.8 ppb, 95% CI 12.0 to 21.5) and also had higher baseline respiratory resistance, lower reactance, and larger bronchodilator responses expressed as the change in resistance after inhalation of salbutamol. Children with chronic cough only (n=46) also had significantly raised mean FE(NO) (9.2 (1.5) ppb; mean difference 3.9 ppb, 95% CI 0.8 to 7.0) but their lung function was not significantly reduced. Children on inhaled steroids due to previously diagnosed asthma (n=29) differed from the controls only in their baseline lung function. The analysis of receiver operating characteristics (ROC) showed that FE(NO) provided the best power for discriminating between children with probable asthma and healthy controls, with a sensitivity of 86% and specificity of 92% at the cut off level of 1.5 SD above predicted. CONCLUSIONS: FE(NO) is superior to baseline respiratory function and bronchodilator responsiveness in identifying preschool children with probable asthma. The results emphasise the presence of airway inflammation in the early stages of asthma, even in young children.

Airway Resistance↗

PubMed2003

Sustained reduction in bronchial hyperresponsiveness with inhaled fluticasone propionate within three days in mild asthma: time course after onset and cessation of treatment.

BACKGROUND: Bronchial hyperresponsiveness (BHR) is characteristic of asthmatic airways, is induced by airway inflammation, and is reduced by inhaled corticosteroids (ICS). The time course for the onset and cessation of the effect of ICS on BHR is unclear. The effect of inhaled fluticasone propionate (FP) on BHR in patients with mild persistent asthma was assessed using time intervals of hours, days and weeks. METHODS: Twenty six asthmatic patients aged 21-59 years were selected for this randomised, double blind, parallel group study. The effect of 250 micro g inhaled FP (MDI) administered twice daily was compared with that of placebo on BHR assessed using a dosimetric histamine challenge method. The dose of histamine inducing a decrease in forced expiratory volume in 1 second (FEV(1)) by 15% (PD(15)FEV(1)) was measured before and 6, 12, 24 and 72 hours, and 2, 4 and 6 weeks after starting treatment, and 48 hours, 1 week and 2 weeks after cessation of treatment. Doubling doses of changes in PD(15)FEV(1) were calculated and area under the curve (AUC) statistics were used to summarise the information from individual response curves. RESULTS: The increase in PD(15)FEV(1) from baseline was greater in the FP group than in the placebo group; the difference achieved significance within 72 hours and remained significant until the end of treatment. In the FP group PD(15)FEV(1) was 1.85-2.07 doubling doses above baseline between 72 hours and 6 weeks after starting treatment. BHR increased significantly within 2 weeks after cessation of FP treatment. CONCLUSIONS: A sustained reduction in BHR to histamine in patients with mild asthma was achieved within 3 days of starting treatment with FP at a daily dose of 500 micro g. The effect tapered within 2 weeks of cessation of treatment.

Administration, Inhalation↗

PubMed2003

Airway inflammation, bronchial hyperresponsiveness and asthma in elite ice hockey players.

There is little information of lower respiratory symptoms, bronchial hyperresponsiveness and airway inflammation in elite ice hockey players. A total of 88 highly trained ice hockey players and 47 control subjects were studied. All the subjects were subjected to skin-prick tests, resting spirometry examinations and histamine-challenge tests. Adequate induced sputum samples were obtained from 68 of the ice hockey players and from 18 symptom-free control subjects on a separate day. Bronchial hyperresponsiveness in a histamine-challenge test was found in 21 (24%) of the athletes and in five (11%) of the controls. Current asthma (current asthmatic symptoms and increased bronchial responsiveness) was observed in 13 (15%) of the athletes and in one (2%) of the control subjects. Total asthma (current asthma or previously physician-diagnosed asthma) occurred in 19 (22%) of the athletes and in two (4%) of the controls. Atopy, according to skin-prick tests, was observed in 51 (58%) of the athletes and 17 (36%) of the control subjects. The differential cell counts of eosinophils (2.6 versus 0.2%) and neutrophils (80.9 versus 29.9%) in the sputum samples of the ice hockey players were significantly higher than in those of the control subjects. Asthma is common in elite ice hockey players and they show signs of a mixed type of neutrophilic and eosinophilic airway inflammation. Inhalation of cold air associated with exposure to indoor pollutants during intensive training is a possible causative factor.

Adolescent↗

PubMed2002

Development of new IgE specificities to allergenic components in birch pollen extract during specific immunotherapy studied with immunoblotting and Pharmacia CAP System.

BACKGROUND: New IgE sensitizations to proteins in allergen extracts have been shown to occur during allergen-specific immunotherapy (IT). However little is known about the kinetics of the changes in antibody reactivities. METHODS: Twenty-four allergic children and adults were treated with birch pollen rush IT (RIT). Fifteen matched patients served as allergic controls. Sera were obtained at regular intervals for up to three years and analyzed with immunoblotting and Pharmacia CAP System with recombinant (r) birch pollen allergens (rBet v 1, rBet v 2, and rBet v 4). RESULTS: All birch-allergic patients had specific IgE to the major birch pollen allergen Bet v 1, but only three had IgE to rBet v 2 and/or rBet v 4 at the beginning of the study. New IgE sensitizations developed in 65% of the birch RIT-treated patients when studied by immunoblotting. Twenty-nine percent of the patients developed new sensitizations to rBet v 2 and/or rBet v 4 during RIT as measured by Pharmacia CAP System. Generally, new specific IgE reactivities occurred after at least one year of RIT, and only at low levels (< 1 kUA/l). CONCLUSIONS: Sensitization to additional allergenic pollen components frequently occurs during prolonged birch RIT. However, the IgE levels are low and the clinical relevance is not known.

Adolescent↗

PubMed2002

No effect of oral treatment with an intestinal bacterial strain, Lactobacillus rhamnosus (ATCC 53103), on birch-pollen allergy: a placebo-controlled double-blind study.

BACKGROUND: Oral probiotic bacteriotherapy with Lactobacillus rhamnosus has given promising results in small children with food allergy. We studied the effects of similar therapy in teenagers and young adults, who were allergic to birch pollen and apple food and had intermittent symptoms of atopic allergy and/or mild asthma. METHODS: We conducted a double-blind, placebo-controlled study, in which respiratory and eye symptoms and use of medications in two groups were compared. Open oral challenge tests with a slice of apple were performed trice: before, during and after the birch-pollen season. There were 18 patients in each group. They used Lactobacillus rhamnosus for 5.5 months; 2.5 months before the pollen season, 1 month during the season (May), and 2 months after. RESULTS: The results were negative. The treatment did not alleviate the symptoms of the patients or reduce their use of medication during the birch-pollen season or the subsequent 2 months. The treatment did not significantly affect the symptoms caused by apple in the oral challenge tests. CONCLUSIONS: We found no indication of a beneficial treatment effect in our patients. As the number of patients was relatively small, conclusions should be drawn with caution.

Administration, Oral↗

PubMed2002

Increase of allergen-specific immunoglobulin E antibodies from 1973 to 1994 in a Finnish population and a possible relationship to Helicobacter pylori infections.

BACKGROUND: The prevalence of atopic diseases--hayfever, asthma and eczema--has increased over the past decades. The increase may be associated with decreased rates of infections such as measles, hepatitis A, tuberculosis, toxoplasmosis, and, as recently suggested, Helicobacter pylori gastritis. OBJECTIVE: Since the increase of atopy has been mainly based on clinical studies, we wanted to study the prevalence of allergen-specific Immunoglobulin (Ig)E antibodies in two cross-sectional, adult population-based serum samples two decades apart. Since the sera had been tested for H. pylori antibodies, we also had a chance to look for a possible relationship between these two findings. METHODS: We determined the prevalence rate of allergen-specific serum IgE antibodies against birch and timothy pollen, and cat and dog epithelium allergens by the radioallergosorbent test in a 15-54-years-old Finnish population using 326 sera collected in 1973 and 319 sera collected in 1994 from randomly selected subjects. RESULTS: From 1973 to 1994 allergen-specific IgE prevalence rates and IgE antibody levels rose. In 1994, the prevalence rate of positive findings in 15-24-year-old population had increased from 11 to 38% (3.5-fold increase, P = 0.0001, OR 5.12, CI 95% 2.32-11.3). In older 10-year age groups similar trends did not reach significance, but the overall change was significant with all three cut-off levels of allergen-specific IgE analysed. The percentage of IgE-positive persons rose mainly in the subgroup with no H. pylori antibodies. In 1994 21% of the H. pylori-negative subjects had IgE antibodies compared with 5% of the H. pylori-positive subjects (in 1973 11% in both subgroups). CONCLUSIONS: IgE-based evidence for an increase in IgE-mediated allergy was uncovered. The increase occurred mainly in the subgroup with no antibodies to H. pylori, which support the hypothesis that H. pylori could be one of the microbes counteracting atopy.

Adolescent↗

PubMed2002

Eosinophilic airway inflammation as an underlying mechanism of undiagnosed prolonged cough in primary healthcare patients.

Prolonged cough is a common problem in patients seen in general practice. Using a simple method of sputum induction and processing of sputum samples, we determined whether eosinophilic airway inflammation could be a cause of undiagnosed prolonged cough. Eighty-two patients who had had cough for more than 1 month were enrolled into the study, in six primary healthcare centres. Patients with known pulmonary disease, including asthma or chronic obstructive pulmonary disease (COPD), or who were known to have another cause of cough, or to have recently suffered from a respiratory infection, were excluded. Fifty-three healthy individuals served as controls. Sputum was induced by inhalation of 3% saline. Inflammatory cells in smears were studied semi-quantitatively. Concentrations of eosinophil cationic protein (ECP), eosinophil peroxidase (EPO), myeloperoxidase (MPO) and human neutrophilic lipocalin (HNL) were determined. Sputum induction proved safe and adequate samples were obtained from 91%. Sputum eosinophilia (eosinophils accounting for more than 5% of all cells in smears) was present in 14 patients with prolonged cough (19%) but in no healthy individual (P=0.001). Five of the 14 individuals (36%) who exhibited sputum eosinophilia appeared to have asthma, while nine of the 14 (64%) did not. Concentrations of ECP and EPO were higher in patients with prolonged cough than in healthy individuals (P=0.02 for ECP; 0.005 for EPO). We conclude that eosinophilic airway inflammation is a fairly common cause of prolonged cough, even in patients not suffering from asthma or COPD, or in whom no other cause of cough is known to be present. Induced sputum samples obtained in health centres can be studied in a central laboratory. Detection of eosinophilic airway inflammation could aid the decision regarding treatment.

Acute-Phase Proteins↗

PubMed2002

Identification of intracellular markers in induced sputum and bronchoalveolar lavage samples in patients with respiratory disorders and healthy persons.

Induced sputum and bronchoalveolar lavage (BAL) are widely used for retrieving cells and soluble materials for studies of airway inflammation. Centrifuged cell samples are suitable for immunochemical identification of cellular products. The aim was to determine the optimal fixation procedure to detect intracellular antigens in situ. In immunocytochemistry, an appropriate choice of fixation method is a prerequisite for identification of cells and, consequently, for reliability results. We compared eight fixation and permeabilization methods to detect intracellular antigens in cytocentrifuged cell samples. Four granular proteins specific to eosinophils (eosinophil cationic protein, ECP; eosinophil peroxidase, EPO) and neutrophils (human neutrophil lipocalin, HNL; myeloperoxidase, MPO) were the antigens studied. We found that the organic solvents often used in immunocytochemistry are unsuitable fixatives for detection of these intracellular low-molecular-weight proteins. Treatment with crosslinking fixatives alone resulted in incomplete penetration of antibodies into the cell interiors. Best results were obtained using a commercial reagent Ortho PermeaFix (OPF) for flow cytometry. With this, fixation and permeabilization take place simultaneously OPF-treated cells retained their structural characteristics, and the antibodies studied penetrated both cellular and granule membranes. With OPF treatment, ECP EPO, HNL, and MPO were fixed on their places in granules, and their antigenicity was retained. Correct identification of intracellular proteins is important in characterization of the respiratory inflammatory response in clinical work and research.

Acute-Phase Proteins↗

PubMed2002

Exercise-induced changes in pulmonary function of healthy, elite long-distance runners in cold air and pollen season exercise challenge tests.

Exercise-induced changes in postexercise pulmonary function have not been studied in healthy elite athletes in normal training conditions. Twelve healthy elite runners volunteered. They showed normal resting spirometry and bronchial responsiveness to histamine, and were non-atopic. They performed free running exercise challenge tests (ECT) at subzero temperature and immediately after highest birch pollen season. The mean maximal postexercise changes in FEV(1), PEF, FVC, and FEV(1)/FVC did not differ between the cold air and pollen season ECTs. Compared with pre-exercise values, FEV(1)increased significantly at 10 min (p = 0.028) and 20 min (p = 0.033) postexercise in the cold air ECT, as well as at 10 min (p = 0.024) and 20 min (p = 0.010) postexercise in the pollen season ECT. The mean (SEM) maximal postexercise change in FEV(1) was mostly small + 2.6 (0.6)% in the winter and + 2.7 (0.9)% in the pollen season. In contrast, significant decreases in PEF, compared with baseline, were found at 10 min (p = 0.071) and 20 min (p = 0.0029) postexercise in the cold air ECT, as well as at 10 min (p = 0.060) and 20 min (p = 0.010) postexercise in the pollen season ECT (p = 0.0076). The mean (SEM) maximal postexercise fall in PEF was 5.9 (1.0)% in the winter and 6.0 (1.8)% in the pollen season. Heavy exercise challenge tests in extreme conditions increased FEV(1) post-exercise, while PEF decreased as compared with pre-exercise values. Thus, even small postexercise falls in FEV(1) may be considered as deviate exercise responses in elite athletes.

Adult↗

PubMed2002

Cell specific markers for eosinophils and neutrophils in sputum and bronchoalveolar lavage fluid of patients with respiratory conditions and healthy subjects.

BACKGROUND: Highly specific protein markers for eosinophils and neutrophils could be a valuable diagnostic aid in various respiratory disorders. The cell specificity of monoclonal antibodies against eosinophil peroxidase (EPO), eosinophil cationic protein (ECP), human neutrophil lipocalin (HNL), and myeloperoxidase (MPO) was investigated using immunocytochemical techniques. METHODS: Induced sputum and bronchoalveolar lavage fluid samples from 14 patients with respiratory conditions and four healthy individuals were studied. Antigens were detected at their intracellular sites in cells with well preserved structures using optimal techniques for fixation, permeabilisation, and immunolabelling. RESULTS: Anti-EPO antibodies reacted only with eosinophils, and anti-HNL antibodies only with neutrophils. Anti-ECP antibodies reacted with both eosinophils and neutrophils and anti-MPO antibodies with neutrophils and monocytes. Cells not stained by monoclonal anti-EPO and anti-HNL antibodies included lymphocytes, monocytes, macrophages, squamous epithelial cells, and ciliated epithelial cells. CONCLUSIONS: EPO, a unique component of eosinophils, and HNL, a unique component of neutrophils, are useful markers for the identification of eosinophils and neutrophils, respectively, in sputum and bronchoalveolar lavage fluid.

Acute-Phase Proteins↗

PubMed2002

The disease management approach to controlling asthma.

Asthma has become an important public health issue worldwide and certain groups, such as children, are at particular risk of the disease. Often asthma remains under-diagnosed and under-treated. Despite these worrying trends, the disease management approach to asthma control can help most asthma patients achieve a 'normal' way of life. The increased prevalence and greater diagnostic awareness of asthma have placed increased demands on healthcare resources, but effective asthma control can minimize the personal, social and economic burdens of asthma. Early diagnosis and immediate anti-inflammatory treatment is the first step in gaining control of symptoms. A stepwise approach is then used to classify asthma severity and treatment, with the number and frequency of medications increasing (step up) as asthma severity increases and decreasing (step down) when asthma is under control. This stepwise approach to asthma management necessitates regular review of treatment once asthma is under control. However, effective asthma management is dependent on successful patient education, adherence to prescribed medication and good doctor patient partnerships. Current treatment guidelines recommend the use of a written asthma management plan that should be agreed between the doctor and patient. These plans should cover all aspects of asthma treatment, including prevention steps for long-term control and action steps to stop attacks once a worsening in asthma has been recognized. This comprehensive approach to asthma management increases the likelihood of achieving asthma control, which in turn reduces the need for emergency visits to the hospital or clinic and reduces the limitations on physical activity previously imposed by the condition.

Administration, Inhalation↗

PubMed2002

Determinants of respiratory system input impedance and bronchodilator response in healthy Finnish preschool children.

In order to study the determinants of respiratory system impedance and bronchodilator response in preschool children, a sample (n = 109) of healthy children (age 2.1-7.0 years) attending kindergarten was measured by using the impulse oscillometry. Their selection was based on a standardized questionnaire, negative skin prick test results and clinical examination, and sufficient cooperation. Triple measurements of respiratory resistance (Rrs) and reactance (Xrs) at 5, 10, 15 and 20 Hz, total respiratory impedance (Zrs), the resonance frequency (Fr) and the frequency dependence of resistance (dRrs/df) were performed, to determine individual mean values. Measurements were repeated after inhalation of 300 microg salbutamol (n = 89) or placebo (n = 19). At the baseline, Zrs and Rrs5-20 showed negative, and Xrs5-20, Fr and dRrs/df positive correlations with age, height and weight. However, logarithmic transformed height was the best independent variable for the regression equations of all the oscillometric variables. After inhalation of placebo, none of the oscillometric variables changed significantly. In the salbutamol group, the mean (SD) change in Rrs5 was -0.187 (0.124) kPa l(-1) s(-1) and -19.2 (10.2)%, corresponding to a lower reference limit of -36.9%. Both the within-test and between-test repeatabilities for the measurement of respiratory resistance were acceptable, for Rrs5 the coefficients of variation being 6.2 and 6.1%, respectively. As the overall success rate in our sample was high (89%), the forced oscillation technique seems to be a useful method in assessing respiratory function and bronchial lability in preschool children.

Administration, Inhalation↗

PubMed2001

Dose-ranging study of mometasone furoate dry powder inhaler in the treatment of moderate persistent asthma using fluticasone propionate as an active comparator.

BACKGROUND: Mometasone furoate (MF; Schering-Plough, Madison, NJ), is a glucocorticoid with high local potency and low potential systemic availability. OBJECTIVES: To compare the relative efficacy and safety of a new formulation of MF, coupled with a recently designed dry powder inhaler (DPI), in the treatment of patients with moderate persistent asthma. Fluticasone propionate administered by Diskhaler (FP Diskhaler, 250 microg twice a day; Glaxo Wellcome, Research Triangle Park, NC) was used as an active control. DESIGN: A randomized, parallel group, double-blind (for MF-DPI dosage), evaluator-blind (for MF-DPI vs FP) trial. SETTING: Sixty centers in 20 countries. PATIENTS: Seven hundred thirty-three patients with moderate persistent asthma on inhaled corticosteroid treatment. INTERVENTIONS: Discontinuation of previous inhaled corticosteroid and initiation of one of four study treatments: three doses of MF-DPI (100, 200, and 400 microg twice daily) and one of FP (250 microg twice daily >12 weeks). RESULTS: FEV1 (primary efficacy variable) was evaluated as the mean change from baseline to endpoint (last evaluable visit). All dosage groups showed improvement at endpoint. Only 400 microg twice daily of MF-DPI (+0.19 L) was statistically different from 100 microg twice daily of MF-DPI (+0.07 L; P = 0.02). MF-DPI (200 microg twice daily) and FP Diskhaler groups showed similar improvement (+0.16 L). Greater improvement in most secondary variables (forced expiratory flow between 25% and 75% of vital capacity, and morning and evening peak expiratory flows) also resulted from treatment with 200 or 400 microg twice daily of MF-DPI or with FP Diskhaler, compared with 100 microg twice daily of MF-DPI. Overall, a total daily 800-microg dose of MF-DPI conferred no significant additional benefit >400 microg of MF-DPI. The incidence of oral candidiasis was 1%, 7%, 10%, and 10% in the 100, 200, and 400 microg twice daily of MF-DPI and FP groups, respectively. CONCLUSIONS: A total daily dose of 400 microg of MF-DPI provides clinical benefit comparable to that observed with a total daily dose of 500 microg of FP Diskhaler.

Administration, Inhalation↗

PubMed2001

Pollen-specific rush immunotherapy: clinical efficacy and effects on antibody concentrations.

BACKGROUND: Studies of rush immunotherapy (RIT) with standardized extracts for the treatment of seasonal pollen allergy are few, especially for birch-pollen RIT. OBJECTIVE: The study was performed to investigate the efficacy of RIT with standardized birch- or timothy-pollen extracts. Further, the serum antibody levels were evaluated for correlation with clinical efficacy. METHODS: This open, longitudinal study included 30 allergic patients treated with RIT and 16 allergic patients serving as a control group. The therapy was continued for 3 years and blood samples were collected at regular intervals for antibody measurements using the Pharmacia CAP System. RESULTS: The RIT was generally well tolerated. An increase in the total and specific IgE concentrations during the early months of RIT was observed, followed by decreased levels. Specific IgG and IgG4 increased continuously for 2 years. The symptom and medication scores were significantly decreased, compared with preRIT, at both the first and third pollen seasons after the start of RIT treatment (P < .0001 and P < .001, respectively). The clinical improvement during RIT was significantly greater compared with the control group (P < .05). The decreased medication and the symptom improvement during the third year of RIT correlated with the relative decrease in specific IgE (rs = .52, P < .05) and with the specific IgG4 level before the start of RIT (rs= -.68, P < .01), respectively. CONCLUSIONS: Our study indicates that RIT with standardized birch- or timothypollen extracts is clinically effective and safe. Measurements of specific antibody levels during treatment may be helpful in monitoring RIT.

Adult↗