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PubMed1996

Asthma on Tristan da Cunha: looking for the genetic link. The University of Toronto Genetics of Asthma Research Group.

Although asthma has a significant heritable component, the mode of inheritance remains controversial because of the complexity of the disease and the influence of environmental factors. Isolated, inbred populations serve to reduce variability, thus increasing the probability of gene localization. We studied the inbred population of the remote island of Tristan da Cunha to document asthma prevalence for the purpose of genetic linkage analysis. Medical histories and skin atopy were determined on 282 islanders, representing 97% of the population, and airway responsiveness was measured in 254; 226 by methacholine challenge (tidal breathing method) and 28 by bronchodilator response (400 micrograms salbutamol aerosol). Blood samples were collected from 275 islanders. Participants ranged in age from 3 to 94 yr. Asthma was defined as increased airway responsiveness (AR+: PC20 < 4 mg/ml or > or = 15% increase in FEV1 postbronchodilator) combined with a positive history (Hx+). Fifty-seven percent of the islanders had at least partial evidence of asthma (Hx+ and/or AR+) and 23% had a definitive diagnosis of asthma (AR+ with Hx+). Overall 47% of the population were atopic, atopy was proportionally higher in asthmatics (74%) than nonasthmatics (32%; p < 0.01). Analysis of the methacholine dose-response curves demonstrated that asthmatics were significantly (p < 0.01) more responsive than those with AR+ only, and nonasthmatics (AR-, Hx-) were more responsive than laboratory control subjects (p < 0.05), suggesting that these islanders may also carry an airway hyperresponsiveness gene. A frequency plot of the percent fall in FEV1 for all Hx- subjects compared with control data suggests a bimodal distribution consistent with a major gene mechanism for airway responsiveness. Genealogy mapping revealed that the islanders are direct descendants of the 15 original settlers, and historical records suggest at least two founders may have been asthmatic. The data confirm previous reports of a high asthma prevalence on Tristan and support the postulate that this prevalence is a result of gene enrichment occurring in isolated populations by virtue of extensive inbreeding and a probable founder effect.

Adolescent↗
PubMed1996

National Asthma Education and Prevention Program working group report on the financing of asthma care.

The financing of asthma care is the third topic of the National Asthma Education and Prevention Program Task Force Report on the Cost Effectiveness, Quality of Care, and Financing of Asthma Care. This working group explored the effects of financing on access to services, treatment of asthma, and potential health outcomes. Over the course of a year, the working group collected and analyzed information pertaining to the various types of public and private health care financing mechanisms, including both insurance-based and non-insurance-based issues. The group examined the published literature and gathered information from four public hearings conducted across the nation. The result of this synthesis of information on health care financing and asthma care is a set of 12 recommendations that seek to improve the financing of asthma care.

Asthma↗
PubMed1980

The prevalence and incidence of asthma and asthma-like symptoms in a general population sample.

We have examined the prevalence of incidence of asthma and other wheezing syndromes in subjects in a longitudinal epidemiologic study. The point prevalence of asthma was 6.6%, with the highest rates occurring in children. Rates were also relatively high in older subjects, in most of whom "chronic bronchitis and/or emphysema" had been concomitantly diagnosed. Other wheezing was very common in this population sample; in most age groups, the point prevalence rates of some form of wheezing exceeded 30%. New asthma developed in 1.4% of the subjects who were followed over a period of approximately 4 yr. New attacks of shortness of breath with wheeze occurred in 10.3% of the subjects at risk over the same time period. The incidence of asthma was greatest in young children, was least in late adolescence, and increased again in early adult life. The incidence was 1.5 times greater in young boys than in young girls but was much greater in women older than 40 yr of age, perhaps reflecting the diagnostic biases of physicians. In subjects younger than 40 yr of age, onset of the disease was strongly associated with previously demonstrated allergy skin test reactivity. New disease in this age group occurred de novo, primarily within the first few years of life or during early adult life. Subjects in whom asthma developed after 40 yr of age usually had prior symptoms of chronic bronchial irritation and often had obvious spirometric abnormalities. The disease in these subjects was not associated with positive allergy skin test reactions. Because in these older subjects it does not appear possible to clearly distinguish "asthma" from "chronic bronchitis," the label "asthmatic bronchitis" appears to be a reasonable descriptive term for this syndrome.

Adolescent↗
PubMed2004

Montelukast reduces asthma exacerbations in 2- to 5-year-old children with intermittent asthma.

The PREVIA study was designed to investigate the role of montelukast, a leukotriene receptor antagonist, in the prevention of viral-induced asthma exacerbations in children aged 2 to 5 years with a history of intermittent asthma symptoms. The study was a 12-month multicenter, double-blind, parallel-group study of patients with asthma exacerbations associated with respiratory infections and minimal symptoms between episodes. Patients were randomized to receive oral montelukast 4 or 5 mg (depending on age) (n = 278) or placebo (n = 271) once per day for 12 months. Caregivers recorded children's symptoms, beta-agonist use, and health care resource use in a diary card. Over 12 months of therapy, montelukast significantly reduced the rate of asthma exacerbations by 31.9% compared with placebo. The average rate of exacerbation episodes per patient was 1.60 episodes per year on montelukast compared with 2.34 episodes on placebo. Montelukast also delayed the median time to first exacerbation by approximately 2 months (p = 0.024), and the rate of inhaled corticosteroid courses (p = 0.027) compared with placebo. Montelukast effectively reduced asthma exacerbations in 2- to 5-year-old patients with intermittent asthma over 12 months of treatment and was generally well tolerated.

Acetates↗
PubMed2003

Dissection of experimental asthma with DNA microarray analysis identifies arginase in asthma pathogenesis.

Asthma is on the rise despite intense, ongoing research underscoring the need for new scientific inquiry. In an effort to provide unbiased insight into disease pathogenesis, we took an approach involving expression profiling of lung tissue from mice with experimental asthma. Employing asthma models induced by different allergens and protocols, we identified 6.5% of the tested genome whose expression was altered in an asthmatic lung. Notably, two phenotypically similar models of experimental asthma were shown to have distinct transcript profiles. Genes related to metabolism of basic amino acids, specifically the cationic amino acid transporter 2, arginase I, and arginase II, were particularly prominent among the asthma signature genes. In situ hybridization demonstrated marked staining of arginase I, predominantly in submucosal inflammatory lesions. Arginase activity was increased in allergen-challenged lungs, as demonstrated by increased enzyme activity, and increased levels of putrescine, a downstream product. Lung arginase activity and mRNA expression were strongly induced by IL-4 and IL-13, and were differentially dependent on signal transducer and activator of transcription 6. Analysis of patients with asthma supported the importance of this pathway in human disease. Based on the ability of arginase to regulate generation of NO, polyamines, and collagen, these results provide a basis for pharmacologically targeting arginine metabolism in allergic disorders.

Animals↗
PubMed2000

Enhancing care for people with asthma: the role of communication, education, training and self-management. 1998 World Asthma Meeting Education and Delivery of Care Working Group.

Reduction in the morbidity associated with asthma requires attention to several aspects of the behaviour of health professionals and patients, and to the interactions between these two groups. In this review, what has been learnt about health professional/patient communication and patient education (skills, settings and materials), lay and health professional liaison (including telephone helplines), patient education in low-income countries, the integration of patient education into clinical practice, health professional training and the implementation of guidelines, and the role of national asthma campaigns is drawn together. What changes in public policy would enhance asthma care, and whether the promotion of asthma self-management skills is cost effective are also considered. It is concluded that, although further research is necessary in many areas, well-educated health professionals who recognize the person with asthma as an individual, and who give advice about self-management, can significantly reduce the suffering and costs associated with asthma.

Asthma↗
PubMed2002

The anti-IgE antibody omalizumab improves asthma-related quality of life in patients with allergic asthma.

The aim of the present study was to determine the effect of treatment with omalizumab, an anti-immunoglobulin E antibody, on asthma-related quality of life (AQoL) in patients with moderate-to-severe allergic asthma. A total of 546 patients with allergic asthma were randomised to double-blind subcutaneous treatment with either placebo or omalizumab for 52 weeks. A constant beclomethasone dipropionate dose was maintained during the first 16 weeks (steroid-stable phase). This was followed by a 12-week steroid-reduction phase. The core study was followed by a 24-week double-blind extension phase. AQoL was evaluated at baseline and at the end of the steroid-stable (week 16), steroid-reduction (week 28) and extension phases (week 52) using the Juniper Asthma Quality of Life Questionnaire (AQLQ). Baseline AQLQ scores were comparable for the two treatment groups. Relative to placebo, omalizumab-treated patients demonstrated statistically significant improvements from baseline across all four AQLQ domains, as well as overall AQoL score, at weeks 16 (except environmental exposure), 28 and 52. Patients on omalizumab were also more likely to achieve clinically significant improvements in AQoL during the course of the study. Overall, almost 70% of patients and investigators rated treatment with omalizumab as "excellent/good", compared with approximately 40% of placebo recipients. Clinical studies show that omalizumab enhances disease control whilst reducing corticosteroid consumption in patients with allergic asthma. The results of the present study show that these changes are paralleled by improvements in asthma-related quality of life that are meaningful to such patients.

Administration, Inhalation↗
PubMed2005

Alveolar nitric oxide in adults with asthma: evidence of distal lung inflammation in refractory asthma.

Recent studies have suggested that alveolar nitric oxide (NO) concentration is a noninvasive test of distal lung inflammation. The current study determined whether alveolar NO concentration can be measured in patients with asthma of varying severity, tested the hypothesis that there is an association between alveolar NO and bronchoalveolar lavage (BAL) eosinophil count and determined whether refractory asthma is characterised by a raised alveolar NO concentration. Finally, the present authors assessed the effect of 2 weeks of prednisolone (30 mg q.d.) on alveolar NO concentration. Alveolar NO concentration was both measurable and repeatable in patients with refractory asthma. A positive correlation was found between alveolar NO concentration and BAL eosinophil count but not with bronchial wash or sputum eosinophil count. Alveolar NO concentration was increased in patients with refractory asthma (7.1 ppb) compared with mild-to-moderate asthma (3.4 ppb) and normal controls (3.4 ppb) and reduced by treatment with prednisolone. In conclusion, these findings support the hypothesis that alveolar nitric oxide is a measure of distal airway inflammation and suggest that distal lung inflammation is present in refractory asthma.

Administration, Inhalation↗
PubMed1998

Are International Asthma Guidelines effective for low-income Brazilian children with asthma?

The present study was designed to evaluate the effectiveness of International Asthma Guidelines in low-income asthmatic children in the city of São Paulo, Brazil. Fifty children with moderate or severe asthma were evaluated. Patients were evaluated before and after a 1 yr follow-up period using a pre- and post-education design with patients acting as their own controls. Parents were interviewed before and 1 yr after the programme. Most of the children were receiving inadequate medical care from their primary physicians, based mainly on bronchodilators. After the educational programme combined with a medical treatment based mainly on inhaled steroids, there was a decrease in emergency room visits and no need for hospital admissions. There was also a significant decrease in asthma severity and impairment scores (p<.0001). The combination of good medical care and an educational programme can reduce the symptoms of asthma and significantly increase the quality of life, as well as decreasing the costs of asthma treatment. We conclude that by applying the International Asthma Guidelines substantial success was achieved, resulting in moving the patients from crises-orientated management into a chronic care and preventive management mode.

Adolescent↗
PubMed2000

Comparison of asthma prevalence in the ISAAC and the ECRHS. ISAAC Steering Committee and the European Community Respiratory Health Survey. International Study of Asthma and Allergies in Childhood.

International and regional prevalence comparisons are required to test and generate hypotheses regarding the causes of increasing asthma prevalence in various age groups worldwide. The International Study of Asthma and Allergies in Childhood (ISAAC) is the first such study in children and the European Community Respiratory Health Survey (ECRHS) is the first such study in adults. Therefore, a comparison of the findings of these two surveys was conducted, for the 17 countries in which both surveys were undertaken. There was a strong correlation between the ISAAC and ECRHS prevalence data, with 64% of the variation at the country level, and 74% of the variation at the centre level, in the prevalence of "wheeze in the last 12 months" in the ECRHS phase I data being explained by the variation in the ISAAC phase I data. There was also generally good agreement in the international patterns observed in the two surveys for self-reported asthma (74% of country level and 36% of centre level variation explained), self-reported asthma before age 14 yrs (64 and 26%), hay fever (61 and 73%) and eczema (41 and 50%). Thus although there were differences in the absolute levels of prevalence observed in the two surveys, there is good overall agreement between the International Study of Asthma and Allergies in Childhood and European Community Respiratory Health Survey study findings with regard to international prevalence patterns. These findings, therefore, add support to the validity of the two studies, which provide a new picture of global patterns of asthma prevalence from child- to adulthood, and identify some of the key phenomena which future research must address.

Adolescent↗
PubMed2004

High-resolution CT findings in patients with near-fatal asthma: comparison of patients with mild-to-severe asthma and normal control subjects and changes in airway abnormalities following steroid treatment.

STUDY OBJECTIVES: Extensive airway inflammation and excessive mucus production are implicated in deaths from asthma. High-resolution CT (HRCT) can be used to image both large and small airway abnormalities in asthmatics. The aims of this study were to clarify the distinction of HRCT features between near-fatal asthma (NFA) and non-NFA, and to evaluate serial follow-up HRCT scans of patients with NFA. PATIENTS AND DESIGN: Abnormalities of the large airway (bronchial wall thickness) and small airways (prominence of centrilobular structures and air trapping) were measured semiquantitatively on HRCT scans of 24 non-NFA, 16 NFA, and 16 control subjects. In addition, these abnormalities were reevaluated after intensive and relatively long-term (> 6 months) treatment with inhaled corticosteroids. RESULTS: Prominence of centrilobular structures was observed in 36% of mild asthma cases, in 70% of moderate-to-severe asthma cases, and in 100% of NFA cases. Prominence of centrilobular structures, but neither bronchial wall thickness nor the area of air trapping, was significantly increased in NFA, as compared with mild or moderate-to-severe asthma (p < 0.05). In the seven non-NFA and five NFA patients who underwent follow-up HRCT scans, only bronchial wall thickness was decreased significantly in the NFA cases (p < 0.05), while bronchial wall thickness and the prominence of centrilobular structures were significantly decreased in the non-NFA cases. These small airway abnormalities were partially reversible in the both groups. Residual prominence of centrilobular structures after long-term inhaled corticosteroid treatment was significantly higher in NFA than non-NFA patients. CONCLUSIONS: The results of our study indicate that extensive small airway abnormalities may be associated with NFA, and that these abnormalities are partially reversible after the successful control of asthma symptoms.

Acute Disease↗
PubMed2002

Omalizumab improves asthma-related quality of life in children with allergic asthma.

BACKGROUND AND OBJECTIVE: Omalizumab is a recombinant, humanized, monoclonal anti-immunoglobulin E (IgE) antibody, developed for the treatment of IgE-mediated diseases. In children with allergic asthma, it was shown to reduce the requirement for inhaled corticosteroids while protecting against disease exacerbation. Here we report the effects of treatment with omalizumab on asthma-related quality of life (AQoL) in children with allergic asthma. METHODS: This evaluation was part of a previously reported 28-week, randomized, double-blind, placebo-controlled study to assess the efficacy, safety, and tolerability of omalizumab (at least 0.016 mg/kg/IgE [IU/mL] per 4 weeks) in children with allergic asthma who were well controlled on daily treatment with inhaled corticosteroids. Dosage of beclomethasone dipropionate was kept constant for 16 weeks (steroid-stable phase), then reduced over 8 weeks to the minimum effective dose (steroid-reduction phase). This dose was then maintained for the final 4 weeks. The Pediatric Asthma Quality of Life Questionnaire (PAQLQ) was administered at baseline, week 16, and week 28. RESULTS: Baseline demographics, PAQLQ scores, and other data were comparable for the 2 treatment groups. At the end of the steroid-reduction phase, patients in the omalizumab-treated group reported significant improvements in the "activities" and "symptoms" domain scores as well as overall AQoL compared with placebo. More patients in the omalizumab group achieved clinically relevant (> or =0.5) changes in PAQLQ scores during the course of the study, and this difference was significant for activities and overall AQoL. CONCLUSION: Omalizumab improves AQoL in children with allergic asthma.

Anti-Asthmatic Agents↗
PubMed2006

Improving pediatric asthma care through surveillance: the Illinois Emergency Department Asthma Collaborative.

OBJECTIVES: To better understand and improve the care of asthma patients who require emergency department (ED) care, the Illinois Emergency Department Asthma Collaborative (IEDAC) was created to develop, test, and disseminate an ED-based surveillance system. This report describes the development and testing of the pediatric IEDAC surveillance instruments and demonstrates how these instruments can be used to describe the health status, healthcare delivery, and outcome of children using ED services. METHODS: A convenience sample of 128 children presenting to 5 EDs in Illinois for asthma care was the study base. Data were collected on monthly samples of children aged 2 through 17 years who presented to these EDs from May to November 2003. Three instruments were used to collect data regarding the children's pre-ED, ED, and post-ED experience. RESULTS: At the ED visit, 73.4% of children met national guideline criteria for persistent-level asthma symptoms. Among this group, 53.2% were using inhaled corticosteroid (ICS) medications. At 1 month follow-up, 66.6% of the children met the criteria for persistent-level asthma symptoms, which was statistically unchanged from the ED visit. Among the latter group, 64.2% were using ICS medications, again statistically unchanged compared with the ED visit. At follow-up, 24.5% of children were reported to have returned to an ED or were subsequently hospitalized. The majority of children were noted at follow-up to have limitation of at least some activity. CONCLUSIONS: Children who presented to IEDAC EDs were found to have a high level of asthma burden that continued at follow-up despite treatment. Moreover, a substantial proportion of children had returned to an ED or were subsequently hospitalized. Encouraging trends in medication use were observed, although suboptimal medication use was also observed.

Adolescent↗
PubMed2004

[Prevalence of asthma and asthma symptoms among 13 and 14-year-old schoolchildren, Brazil].

OBJECTIVE: Before the use of the ISAAC (International Study of Asthma and Allergies in Childhood) questionnaire in epidemiologic surveys, little could be told about the comparative occurrence of asthma in the world due to differences in employed methods. In Brazil, the ISAAC questionnaire has been used in some urban regions. In this study it was applied in both, urban and rural areas, in order to estimate the prevalence of asthma among schoolchildren living in Montes Claros, Brazil. METHODS: A cross-sectional study was carried out using the ISAAC written questionnaire with four questions added on exposures of interest. The questionnaire was self-applied in 3,770 randomly selected schoolchildren aged 13 and 14 years. RESULTS: The prevalence of "wheezing in the last year" was 15.8%, and "asthma or bronchitis ever" was 23.8% with no statistically significant difference between boys and girls. There were significant differences between girls and boys regarding "wheezing ever" (37.8% and 33.6%), "sleeping disturbed by wheezing" (13.7% and 9.5%), and "nocturnal dry coughing without respiratory infection" (36.6% and 28.7%), respectively. "Wheezing in the last year" was found to be positively associated with "pet contact" (OR=1.27; 95% CI: 1.03-1.56), and "family history of asthma" (OR=1.79; 95% CI: 1.50-2.14), and negatively associated with "rural school" (OR=0.63; 95% CI: 0.44-0.91). But no association was found with sex, age, private/public school, and passive smoking. CONCLUSIONS: The prevalence of asthma in Montes Claros was high and some symptoms were seen mainly among girls. The occurrence of "wheezing in the last year" showed to be associated with family history, contact with pets and urban schools.

Adolescent↗
PubMedDate not supplied

Malignant potentially fatal asthma: achievement of remission and the application of an asthma severity index.

Patients fulfilling diagnostic criteria for malignant potentially fatal asthma require aggressive involvement by the physician to prevent avoidable fatalities from asthma. Efforts to overcome barriers to treatment caused by noncompliance are critical to successful care. This report reviews five patients with malignant potentially fatal asthma in remission, in whom noncompliance played the major role in preventing control of asthma. Through patient confrontation and the monitoring of serum concentrations of prednisone and its metabolite prednisolone, noncompliance may be addressed. Psychiatric referral may also be of benefit, if accepted by the patient and family. Use of injectable methylprednisolone may be a necessary alternative to prevent life-threatening complications of asthma. In all patients, keeping medical regimens as simple as possible is advocated, with the use of the lowest doses of medication necessary to maintain the control of symptoms, and the prevention of morbidity and mortality. An asthma severity index for the illustration of longitudinal disease severity is applied to these patients.

Adolescent↗
PubMed2000

Compliance during long-term treatment with fluticasone propionate in subjects with early signs of asthma or chronic obstructive pulmonary disease (COPD): results of the Detection, Intervention, and Monitoring Program of COPD and Asthma (DIMCA) Study.

In a prospective study, we investigated the long-term compliance to fluticasone propionate (FP) by dry powder inhalation (Rotadisk) in subjects with early signs of asthma and chronic obstructive pulmonary disease (COPD) without an established diagnosis. Subjects were selected from a large screening program on early stages of asthma and COPD (Detection, Intervention, and Monitoring Program of COPD and Asthma [DIMCA] program) in the general practice. Forty-eight adult subjects with "early signs of COPD" (slightly increased forced expiratory volume in 1 sec [FEV1] decline of >0.04L/year) and 29 adult subjects with "early signs of asthma" (signs of bronchial hyperresponsiveness or reversibility) participated in a randomized placebo-controlled trial with FP (Flixotide 500 microg daily) versus placebo with a duration of 2 years or 1 year, respectively. Compliance was measured by counting Rotadisks returned. By means of a questionnaire, participants were asked about perceived effects and/or side effects of the trial drug. The mean overall individual compliance rates of 72% (range 7%-102%) in the early COPD trial and 71% (range 8%-99%) in the early asthma trial were maintained throughout the study. Perceived effectiveness (12% of the participants) or side effects (30% of the participants) of the trial drug were not related to compliance. The willingness of patients to use the trial drug in daily practice if efficacy would be proved was statistically significantly related to compliance during the trial (p = 0.017). It was concluded that the compliance rates found were relatively high in patients with symptoms of mild asthma or COPD without an established diagnosis. Conviction of the importance of treatment influenced compliance more positively than perceived (side) effects. These results again emphasize the importance of patient education in establishing early treatment with inhaled corticosteroids.

Administration, Inhalation↗
PubMed1995

Effectiveness of a specialized asthma clinic in reducing asthma morbidity in an inner-city minority population.

Asthma is the most common chronic disease of childhood and a leading cause of morbidity in adults. Despite significant advances in medical therapy, asthma morbidity and mortality rates have risen dramatically over the past two decades, especially in minority and socioeconomically disadvantaged populations. Numerous intervention programs have been designed in an attempt to reduce asthma morbidity but few have targeted poor or minority populations. The purpose of this study was to assess whether an outpatient intervention program specifically targeted at a high-minority population in East Harlem, in New York City, was successful in reducing asthma morbidity. A retrospective chart review of 84 patient records was conducted. The patients were divided into two groups, an intervention group (n = 45), who were followed by an asthma specialist (allergist/immunologist), and a nonintervention group, followed by a general internist or pediatrician. Outcome variables including clinic walk-in visits, emergency room visits, and hospitalizations were determined and compared in the pre- and postintervention period in both groups. Patients in the intervention group had reduced total walk-in visits (73 vs. 27, p < 0.001), emergency room visits (30 vs. 5, p < 0.001), and hospitalizations (16 vs. 2, p < 0.001). In contrast, patients in the nonintervention group had no change in total walk-in visits (88 vs. 72), increased emergency visits (7 vs. 22, p < 0.05), and no change in hospitalizations (5 vs. 2), respectively. The outpatient intervention program has been successful in reducing asthma morbidity in the high-risk minority community of East Harlem. Future larger studies are warranted to extend this pilot program to other high-risk minority populations.

Adolescent↗
PubMed1997

Aspirin-induced asthma as a risk factor for asthma mortality.

We have recently reported severe airway obstruction and bronchial hyperresponsiveness (BHR) in fatal asthma compared with patients without a history of near-fatal asthma. Based on these findings, we evaluated whether aspirin-induced asthma (AIA) is a risk factor for asthma mortality by analyzing pulmonary function and BHR. FEV1.0% and methacholine inhalation threshold were significantly lower in the fatal asthma group compared with the AIA and non-AIA groups. However, there were no significant differences between the AIA and non-AIA groups. Our results suggested that AIA is not a risk factor for asthma mortality if avoidance of aspirin and aspirin-like drugs is assured.

Adult↗