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PubMed1995

Lack of effectiveness of magnesium in chronic stable asthma. A prospective, randomized, double-blind, placebo-controlled, crossover trial in normal subjects and in patients with chronic stable asthma.

BACKGROUND: Magnesium sulfate has been helpful in the treatment of acute exacerbations of asthma. We hypothesized that magnesium would also be an effective bronchodilator in patients with chronic stable asthma. METHODS: We performed a prospective, randomized, double-blind, placebo-controlled, crossover trial in 15 patients with chronic, stable asthma and 10 nonasthmatics. On study day 1, spirometry and albuterol challenge were used to confirm the presence of asthma according to American Thoracic Society criteria. On study day 2, subjects received intravenous magnesium sulfate (2 g) or placebo (saline). On study day 3, subjects were crossed over to receive the other drug. Spirometry was performed before, during, and after drug or placebo administration. Circulating ionized magnesium concentrations were determined before and after intravenous magnesium or placebo administration. RESULTS: Magnesium infusion caused no statistically significant changes in forced expiratory volume in 1 second (mean +/- SEM, 1.92 +/- 0.13 L before, 1.98 +/- 0.12 L during, and 2.01 +/- 0.14 L after magnesium administration), forced vital capacity (mean +/- SEM, 3.44 +/- 0.25 L before, 3.60 +/- 0.26 L during, and 3.59 +/- 0.25 L after magnesium administration), or maximum forced expiratory flow rate (mean +/- SEM, 5.42 +/- 0.44 L/second before, 5.46 +/- 0.46 L/second during, and 5.57 +/- 0.49 L/second after magnesium administration). Placebo caused no changes in these three physiologic variables. CONCLUSION: Magnesium is not effective as a bronchodilator in chronic, stable asthmatics or in normal non-asthmatic adults.

Adult↗
PubMed1995

Involvement of thromboxane A2 in bronchial hyperresponsiveness of asthma. Kanazawa Asthma Research Group.

It has been considered that thromboxane A2 (TXA2) is involved in the development of bronchial hyperresponsiveness (BHR), a characteristic feature of asthma. To ensure the involvement of TXA2 in BHR of asthma, effects of a 1-week treatment with two orally active TXA2 antagonists, BAY u 3405 and S-1452, on BHR were examined in 10 and 13 patients with stable asthma, respectively, in two consecutive double-blinded, randomized, placebo-controlled, two-phase crossover studies. Provocative concentration of methacholine causing a 20% fall in FEV1 (PC20-FEV1) with BAY u 3405 (0.78 (GSEM, 1.50) mg/ml) was significantly greater than the value with placebo (0.65 (GSEM, 1.46) mg/ml) (ratio 1.23 times, 95% CI 1.01 to 1.46: P = 0.0401). PC20-FEV1 was also significantly increased with S-1452 (0.43 (GSEM, 1.39) mg/ml) compared with placebo (0.29 (GSEM, 1.27) mg/ml) (ratio 1.75 times, 95% CI 1.05 to 2.45: P = 0.0189). Baseline pulmonary function was not altered by these treatments. These results may ensure that TXA2 is significantly involved in the BHR of asthma while the degree of contribution may be small.

Adolescent↗
PubMed1994

The reproducibility of the Childhood Asthma Questionnaires: measures of quality of life for children with asthma aged 4-16 years.

This paper reports the internal consistency and reproducibility of the Childhood Asthma Questionnaires, measures of quality of life and symptom distress in paediatric asthma. A total of 535 children aged 4-16 years completed age appropriate forms of the questionnaire, over 1- or 3-week intervals. Pearson correlation coefficients between 0.63 and 0.84 for subscales of the questionnaires indicated good test-retest reliability while intraclass correlation coefficients in a very similar range showed that scores also remained at the same level on the two occasions. Comparisons between children with asthma and healthy non-asthmatics indicate that these are likely to be true estimates of stability. Internal consistency varied widely but was higher for older children and longer subscales. Implications of the findings for the use of the questionnaires in the evaluation of new asthma treatments are discussed.

Adolescent↗
PubMed1985

How well do asthma clinic patients understand their asthma?

Fifty asthmatic patients attending a hospital asthma clinic were interviewed to determine their understanding of their asthma and its treatment. Serious defects were found in their ability to judge the severity of their asthma, in their knowledge of medication, and in the correct action to take when deterioration in control occurred. Several risk factors previously identified in studies of asthma deaths were also present in this living population--in particular, delay in seeking medical help until critically ill, and lack of awareness of danger signs. There was evidence of poor patient-doctor contact and unsuccessful patient education.

Adrenal Cortex Hormones↗
PubMed1988

Allergy in asthma. II. The highly atopic infant and chronic asthma.

The relationship between allergy and asthma in infants and preschool children was investigated. One hundred nine children, median age 2 1/2 years, were examined immunologically by quantitation of serum IgE, RAST testing to 13 allergens, and culture of peripheral blood lymphocytes for spontaneous IgE formation. We examined a cross-section of infants and toddlers to determine whether the severity of asthma is associated with allergy as has been reported in older children with asthma. We identified a group of highly atopic infants and preschool children who have serum IgE at least 10 times the mean + 1 SE for age, multiple positive RASTs with early formation of IgE to inhalant antigens, and circulating B cells that spontaneously form IgE when these are cultured in vitro. Such highly atopic infants and preschool children were statistically more likely to have chronic asthma requiring multiple continuous medication compared to the rest of the population (p less than 0.01).

Asthma↗
PubMed2006

A randomized, double-blind trial of the effect of anti-asthma treatment on lung function in children with asthma.

BACKGROUND: Pulmonary function tests (PFTs) and especially spirometry measures are useful tools in evaluating early response to treatment of asthma in children mainly due to their worldwide availability. The aim of our study was to determine the effects of anti-asthma treatment in children, equally on FEV(1), FEF25-75%, R(int) and SR(aw) values. METHODS: Children 6-18 years of age with moderate atopic asthma were randomized to 4-week, placebo-controlled, double-blind trial. Patients were randomly allocated to receive 200 microg budesonide (B) (n=29), 5 or 10 mg (according to age) montelukast (M) (n=29), 200 microg B + 5 or 10 mg M (n=29), 200 microg B + 9 microg formoterol (F) (n=29) or placebo (n=27). FEV(1,) FEF25-75%, R(int), SR(aw) were measured before and after treatment. RESULTS: R(int), SR(aw), FEV(1) improved significantly in all active treatment groups while FEF25-75% improved significantly only in BM group and M group. Combination therapy, showed significantly greater effects on R(int) than monotherapy: BM group compared to B group (P=0.01) and M group (P=0.03) and BF group compared to B group (P=0.01) and M group (P=0.04). CONCLUSION: This study shows that using single parameter for monitoring asthma can be misleading. Using combination of lung function techniques provides better assessment of treatment. Results of our study confirm this hypothesis. The best effect on large and small airways was achieved with combined anti-inflammatory therapy.

Acetates↗
PubMed1998

A comparative study of the effects of ketotifen, disodium cromoglycate, and beclomethasone dipropionate on bronchial mucosa and asthma symptoms in patients with atopic asthma.

Asthma is a chronic inflammatory disorder of the airways that is characterized by infiltration of many inflammatory cells into the bronchial mucosa. We compared the effects of ketotifen, disodium cromoglycate (DSCG), and beclomethasone dipropionate (BDP) on inflammatory cells in the bronchial mucosa and on the asthma symptoms of patients with atopic asthma. In this 12-week parallel study, 32 patients were randomly allocated to either the ketotifen group (2 mg day-1, n = 13), DSCG group (8 mg day-1, n = 9) or BDP (400 micrograms day-1, n = 10). Each subject recorded daily asthma symptoms and peak expiratory flow (PEF). Before and after treatment, pulmonary function and bronchial responsiveness to methacholine were evaluated, and fibreoptic bronchoscopy and biopsy were performed before and after treatment. Biopsy specimens were obtained by bronchoscopy. We performed immunohistochemistry using specific monoclonal antibodies for activated eosinophils (EG2), mast cells (AA1), and T cells (CD3, CD4, and CD8). Our clinical findings showed significant improvement in symptom score and bronchial responsiveness (P < 0.01) each) in all groups. Both the DSCG and the BDP groups had significantly better symptom scores than the ketotifen group (P < 0.05, both groups). PEF significantly increased in the DSCG group in comparison to the ketotifen (P < 0.01) and BDP (P < 0.05) groups, FEV1% increased significantly in the DSCG (P < 0.01) and BDP (P < 0.05) groups in comparison to the ketotifen group. Compared with their baseline values, treatment significantly decreased EG2+ activated eosinophils, and CD3+ and CD4+ T cells, in each group (P < 0.01). Both the DSCG (P < 0.05) and the BDP groups (P < 0.01) exhibited significant decreases in AA1+ mast cell count, but this was not observed in the ketotifen group. Comparing before- and after-treatment values, only the DSCG group exhibited a significant decrease in the number of CD8+ T cells (P < 0.01). Ketotifen, DSCG, and BDP all showed anti-inflammatory activity as determined by examination of the bronchial mucosa of asthmatic patients; and both the DSCG and BDP groups had better clinical responses than the ketotifen group.

Adolescent↗
PubMed1999

The effect of high-dose fluticasone propionate and budesonide on lung function and asthma exacerbations in patients with severe asthma.

The purpose of this study was to investigate the comparative efficacy and safety of equal doses of inhaled fluticasone propionate (FP) and inhaled budesonide (BUD) using their respective dry powder inhalers in a population of severe asthmatics requiring high doses of inhaled corticosteroid. This double-blind double-dummy parallel-group study compared the effects of 24 weeks of treatment with FP (2000 micrograms daily via a Diskhaler inhaler; Glaxo Wellcome, Evreux, France) and BUD (2000 micrograms daily via a Turbuhaler inhaler; Astra Pharmaceuticals, Rijswijka, Netherlands) on lung function and asthma exacerbations in 395 patients with asthma. FP was statistically significantly superior to BUD with respect to the percentage of symptom-free days (P = 0.02), the incidence of days free from rescue bronchodilator usage (P = 0.02) and the distribution of change in peak expiratory flow (PEF) expressed as a percentage of the predicted PEF (P = 0.04). During the treatment period FP was statistically significantly superior to BUD for change in forced expiratory volume in 1 sec (FEV1) at 8, 16 and 24 weeks, change in the median daytime symptom score during weeks 5-16, for incidence of symptom-free days and incidence of days free from rescue bronchodilator usage during weeks 17-24. There was no significant difference between FP and BUD with respect to the number of patients experiencing one or more asthma exacerbation (33.8 and 28.4% of patients, respectively). There was, however, evidence that the exacerbations were clinically less severe in patients treated with FP, in that the time to resolution was quicker (11.0 vs. 14.7 days; P = 0.035), mean duration of all exacerbations (for an individual patient) tended to be shorter (18.5 vs. 23.6 days; P = 0.12), the time off work was reduced (4.2 vs. 7.6 days; P = 0.012) and the lowest PEF recorded during the exacerbation was higher (301 vs. 263 l min-1; P = 0.07). There were no clinically relevant differences in the safety (serum cortisol levels, markers of bone turnover, adverse events) of FP and BUD at these microgram equivalent doses. The patients recruited into this study, in retrospect, probably had no need for such high doses of inhaled corticosteroid but, irrespective of this, FP at microgram equivalent doses showed evidence of superior efficacy to BUD with respect to lung function and severity of asthma exacerbations without producing any greater adverse systemic effect.

Administration, Topical↗
PubMed2006

Asthma in older adults: observations from the epidemiology and natural history of asthma: outcomes and treatment regimens (TENOR) study.

BACKGROUND: The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) was a 3-year, multicenter, observational study of 4,756 patients 6 years or older with severe or difficult-to-treat asthma by physician evaluation. More than 280 pulmonologist and allergist sites across the United States participated. OBJECTIVE: To compare health care utilization (HCU), medication use, asthma control, and quality of life (QoL) in older (> or =65 years; n = 566) and younger (18-64 years; n = 2,912) adult patients in TENOR. METHODS: Patients had to be under a physician's care for at least 1 year and have high medication use or HCU in the past year. Heavy smokers (> or =30 pack-years) and patients with cystic fibrosis were excluded. RESULTS: Although older patients in TENOR had worse lung function as measured by decreased percent predicted forced expiratory volume in 1 second (FEV1) (P < .001), they had significantly lower HCU compared with younger patients. They also had higher use of inhaled corticosteroids and better QoL than younger patients. Older patients reported fewer problems controlling their asthma (P < .001) but reported worse communication with their physicians (P = .02). CONCLUSIONS: Older patients in TENOR appeared to do better than younger patients, despite having worse lung function. Older patients in TENOR may have received more aggressive care than older asthmatic patients in other studies, based on a higher use of inhaled and oral corticosteroids. Whether differences in treatment or disease influenced other physiologic or inflammatory outcomes that contribute to the disconnect between HCU and FEV1 awaits further study.

Adolescent↗
PubMed2002

Asthma: the importance of epithelial mesenchymal communication in pathogenesis. Inflammation and the airway epithelium in asthma.

Asthma is a disorder of the airways in which Th-2-mediated inflammation is considered to provide the basis for altered structure and function that leads to bronchial hyper-responsiveness (BHR) and variable airflow obstruction. This linear progression underpinning asthma pathophysiology is questioned on the basis of observations on the pathology of the disease in early childhood, the independent genetic factors that influence atopy and BHR, incomplete responses to treatment with corticosteroids despite powerful anti-inflammatory effects and the recent disappointing results with targeted therapies that almost abolish eosinophilia in the blood and airways and yet produce little effect on the clinical outcomes of asthma. An alternative hypothesis is put forward in which atopy/airway inflammation and altered structure and function of the formed airway elements are parallel but interacting factors. For asthma to develop as a chronic disease, genetic and environmental factors that drive each of these components are required. Fundamental to this is the concept of aberrant signalling between the airway epithelium and underlying mesenchyme and persistent activation of the epithelial mesenchymal trophic unit.

Asthma↗
PubMed2005

[Geographic variation in the prevalence of asthma symptoms in Spanish children and adolescents. International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3, Spain].

OBJECTIVE: To analyze geographic variations in the prevalence of symptoms related to asthma in Spanish children and adolescents. POPULATION AND METHODS: In 2001 and 2002, the Spanish arm of the International Study of Asthma and Allergies in Childhood (ISAAC) Phase 3 collected information on 28 445 children in the age bracket of 6-7 years in 10 metropolitan areas (A Coruña, Asturias, Barcelona, Bilbao, Cartagena, Castellón, Madrid, Pamplona, San Sebastián, and Valencia) and on 31 257 adolescents in the bracket 13-14 years in 11 areas (the previously named areas plus Valladolid). An asthma symptom questionnaire was filled in by parents or the adolescents themselves. Differences in symptoms between geographic areas were analyzed by fitting a logistic regression model. The relationship between symptoms and age was analyzed by linear correlation. RESULTS: The prevalence of recent wheezing (last 12 months) ranged from 7.1% to 12.9% among 6-7-year-olds and from 7.1% to 15.3% among the 13-14-year-olds. The greatest risk of recent wheezing was observed for children in A Coruña (odds ratio [OR] =1.96 in comparison with the area of lowest prevalence; 95% confidence interval [CI], 1.65-2.33) and Bilbao (OR=1.83; 95% CI, 1.54-2.18) and for adolescents in A Coruña (OR=2.38; 95% CI, 2.04-2.79) and Asturias (OR=2.37; 95% CI, 2.03-2.77). A strong correlation (r=0.72) was observed between the prevalence of recent wheezing and age in each of the geographic areas. CONCLUSIONS: Considerable geographic variation in the prevalence of asthma symptoms can be seen in Spain even among young children. Symptoms are more frequent in children and adolescents who live on the Spain s northern Atlantic coast.

Adolescent↗
PubMed2006

Symptom perception in childhood asthma: the role of anxiety and asthma severity.

This study tested the relationship of anxiety and asthma severity to symptom perception. Eighty-six children diagnosed with mild or moderate asthma had symptom perception and pulmonary function measured throughout methacholine challenge (to induce bronchoconstriction). Higher trait anxiety was associated with heightened symptom perception (controlling for pulmonary function) at baseline. Greater asthma severity was associated with blunted symptom perception (controlling for pulmonary function) at the end of methacholine challenge and with a slower rate of increase in symptom perception across methacholine challenge. These results suggest that anxiety plays a role when children's symptoms are mild, whereas medical variables such as severity play a role in perception of changes in asthma symptomatology as bronchoconstriction worsens.

Adolescent↗
PubMed2004

Increasing prevalence of allergic rhinitis but not asthma among children in Hong Kong from 1995 to 2001 (Phase 3 International Study of Asthma and Allergies in Childhood).

There is a worldwide belief that the prevalence of asthma and other allergic diseases is increasing but the measures used in many studies are susceptible to systematic errors. We examined the trend of asthma, allergic rhinitis and eczema prevalence in school children aged 6-7 years in Hong Kong from 1995 to 2001 using standardized ISAAC methodology. There were 4448 and 3618 children participating in 2001 and 1995, respectively. The prevalence of life-time rhinitis (42.4% vs. 38.9%, p < 0.01), current rhinitis (37.4% vs. 35.1%, p < 0.03), current rhinoconjunctivitis (17.2 vs. 13.6%, p < 0.01) and life-time eczema (30.7% vs. 28.1%, p = 0.01) increased significantly. There was no significant change in prevalence of life-time asthma, life-time wheeze and current wheeze albeit a significant increase in severe asthma symptoms. We investigated a number of potential risk factors including sex, family history of atopy, sibship size, birth weight, respiratory tract infections, pet ownership and exposure to tobacco smoke. However, the increases in prevalence of rhinitis and eczema could not be entirely explained by the change of prevalence of these risk factors. The odds ratio OR for the study period remained significantly associated with current rhinitis (OR 1.31, 95% confidence intervals CI 1.17-1.46), current rhinoconjunctivitis (OR 1.63, 95% CI 1.41-1.87) and life-time eczema (OR 1.30, 95% CI 1.16-1.45) after adjustment for these confounding variables using logistic regression model. Further study is warranted to elucidate the factors contributing to the observable change in the prevalence of rhinitis in our population.

Asthma↗
PubMed2003

Migraine and asthma in childhood: evidence for specific asymmetric parent-child interactions in migraine and asthma families.

In spite of the fact that migraine often manifests as a familial disorder, the role of the family in migraine has not been adequately explored. In this study parent-child interactions in 20 families with a child suffering from migraine were analysed and compared with 20 healthy families and 20 families with an asthma child. The families had to solve a puzzle within a limited time. Parent-child interactions within migraine and asthma families were asymmetric, revealing a disease-specific interpersonal context in the family. Communication with the affected child in migraine families was significantly more directive, with more specific instructions and less help, towards migraineurs than with the healthy siblings. Dominance of parents and submissive behaviour of children were the main features of interactions. In asthma families interactions were more conflicting and less cooperative. This study demonstrated a specific, asymmetric, pattern of family interactions predisposing children either to migraine or asthma.

Adolescent↗
PubMed1998

Effect of local standards on the implementation of national guidelines for asthma: primary care agreement with national asthma guidelines.

OBJECTIVE: To assess the level of modification by local primary care doctors of key aspects of the National Asthma Education Program (NAEP) Guidelines for the Diagnosis and Management of Asthma. DESIGN: A random sample of primary care physicians participating in local asthma guideline development. SETTING: Two hospital systems, one based in an urban environment, and a second in a community and rural environment. PARTICIPANTS: Primary care physicians. INTERVENTION: Design of consensus-based local asthma guidelines using a modified Delphi approach. MEASUREMENTS AND MAIN RESULTS: A total of 42 physicians participated in the local guideline development. With few exceptions, the primary care physicians modified in major ways the NAEP Guidelines regarding the role of pulmonary function testing and spirometry. Specifically, the local guidelines did not require peak flow and spirometry measurements as the basis for initiating inhaled steroids as did the national guidelines. All 42 physicians emphasized a clinical diagnosis versus one based on a pulmonary function. Peak flow monitoring was recommended by 35 (83%) of physicians in selected patients only, in contrast to the national guidelines, which emphasized monitoring for all patients routinely and during exacerbations. There was strong agreement with the national guidelines on the role and importance of patient education, and on the indications for the use of inhaled steroids. CONCLUSIONS: Disagreement by primary care doctors with parts of the NAEP guideline is a potential cause for poor compliance and lack of influence on patient care. Recognizing the need to modify or customize guidelines through field testing with local primary care physicians will improve acceptance of national guidelines.

Administration, Inhalation↗
PubMed2002

Influences of partners' views of asthma self-management and family environment on asthmatic adults' asthma quality of life.

Influences of partners' views of the adult asthmatic's self-management and family environment were explored from the perspective of a collaborative care system. Adults (N = 172, 86 couples) completed questionnaires: perceived control of asthma, perceived ability to care for self, asthma quality of life (AQOL), and an asthma opinion survey. Significant relationships between perceptions of adults with asthma (AWA) and partners were found (r ranged from.32 to.74). Multiple regression analysis of partners' perceptions on AWA AQOL yielded a 3-factor solution (R(2) = 39%). Family cohesion had a significant effect on AWA AQOL (F [1, 168] = 4.43, p <or=.04). Clinical implications are discussed.

Adult↗
PubMed2000

Asthma from childhood to adulthood: asthma severity, allergies, sensitization, living conditions, gender influence and social consequences.

The course of asthma severity, clinical allergies, allergic sensitization, changes in living conditions and social outcome were studied prospectively over five follow-up visits from the mean age of 9 to 30 years in a cohort of 28 boys and 27 girls, selected randomly among asthmatic children attending a paediatric outpatient unit. Asthma severity improved from childhood to adulthood, judged by symptom and medication scores and by the number of hospital admissions, but only nine subjects (16%) had been free from symptoms and medication over the last year of follow-up. After adolescence, asthma continued to improve among the males but not among the females. This difference could not be explained by gender differences in the course of clinical allergies or sensitization (skin-prick-tests and RAST) to common inhaled allergens, or by differences in environmental or social conditions. Sensitization to relevant perennial inhaled allergens correlated with asthma severity during adulthood. In general, clinical allergies and sensitization to inhaled allergens adopted during childhood persisted into adulthood. Approximately 10% of the subjects never adopted a clinical allergy or a positive allergy test. The social outcome was good.

Adolescent↗
PubMed2005

The emergency department as an asthma surveillance tool at the community level: a decline in the burden of pediatric asthma in halifax, Canada.

We report pediatric emergency department (PED) asthma visit and inpatient asthma (AS) admission data in our area over a 5-year period. AS visits decreased by 33.9%, AS admissions by 24.6%, both significant compared with the decline in elementary school enrollment. The decrease in asthma visits was due to a decrease in the number of asthmatic patients, not a decline in repeat visits, or use of alternate venues of care. Explanations include a decrease in the burden of disease or an improvement in ambulatory care, but not alternate treatment venues or improvement in acute (PED) care. Readily available, emergency department data are useful in the community surveillance of asthma.

Asthma↗