Several sets of Canadian guidelines for the diagnosis and management of asthma have been published over the past 15 years. Since the last revision of the 1999 Canadian Asthma Consensus Report, important new studies have highlighted the need to incorporate new information into the asthma guidelines.
To review the literature on adult asthma management published between January 2000 and June 2003; to evaluate the influence of the new evidence on the recommendations made in the 1999 Canadian Asthma Consensus Guidelines and its 2001 update; and to report new recommendations on adult asthma management.
Three specific topics for which new evidence affected the previous recommendations were selected for review: initial treatment of asthma, add-on therapies in the treatment of asthma and asthma education. The resultant reviews were discussed in June 2003 at a meeting under the auspices of the Canadian Thoracic Society, and recommendations for adult asthma management were reviewed.
The present report emphasises the importance of the early introduction of inhaled corticosteroids in symptomatic patients with mild asthma; stresses the benefit of adding additional therapy, preferably long-acting beta2-agonists, to patients incompletely controlled on low doses of inhaled corticosteroids; and documents the essential role of asthma education.
The present report generally supports many of the previous recommendations published in the 1999 Canadian Asthma Consensus Report and provides higher levels of evidence for a number of those recommendations.
Urokinase plasminogen activator (uPA) interacts with its receptor on inflammatory and migrating cells to regulate extracellular matrix degradation, cell adhesion, and inflammatory cell activation. It is necessary for the development of an appropriate immune response and is involved in tissue remodeling. The PLAU gene codes for this enzyme, and is located on 10q24. This region has demonstrated evidence for linkage in a genome scan for asthma in a sample from northeastern Quebec. Here, we hypothesized that uPA may function as a regulator of asthma susceptibility.
To test for association between asthma and genetic variants of PLAU.
We sequenced PLAU and tested for genetic association between identified variants and asthma-related traits in a French-Canadian familial collection (231 families, 1,139 subjects). Additional association studies were performed in two other family-based Canadian cohorts (Canadian Asthma Primary Prevention Study [CAPPS], 238 trios; and Study of Asthma Genes and the Environment [SAGE], 237 trios).
In the original sample, under the dominant model, the common alleles, rs2227564C (P141) and rs2227566T, were associated with asthma (p = 0.011 and 0.045, respectively) and with airway hyperresponsiveness (AHR) (p = 0.026 and 0.038, respectively). Analysis of the linkage disequilibrium pattern also revealed association of the common haplotype for asthma, atopy, and AHR (p = 0.031, 0.043, and 0.006, respectively). Whereas no significant association was detected for PLAU single-nucleotide polymorphisms in the CAPPS cohort, association was observed in the SAGE cohort between the rs4065C allele and atopy under additive (p = 0.005) and dominant (p = 0.0001) genetic models.
This suggests a role for the uPA pathway in the pathogenesis of the disease.
The primary aim of this population-based study was to determine if arterial stiffness is associated with cardiovascular disease (CVD) risk factor clustering and physical activity in youth 12-14 years old. We hypothesized that arterial stiffness would be positively associated with CVD risk factor clustering and negatively associated with physical activity in a dose-response manner in this cohort of youth.
This was a cross sectional study of 485 youth recruited from the 1995 Manitoba birth cohort. The primary outcome, arterial stiffness, was assessed noninvasively using conventional pulse wave analysis and velocity. The primary exposure variables included 1) a measure of cardiometabolic risk, defined as a composite of novel and traditional risk factors for cardiovascular disease and type 2 diabetes and 2) self-reported physical activity.
Neither cardiometabolic risk factor clustering, nor physical activity were associated with either measure of arterial stiffness in this cohort of youth 12-14 years. Cardiometabolic risk decreased with increasing levels of vigorous physical activity, (P
Avoidance of individual risk factors have not been successful in preventing the development of asthma.
We sought to determine the effectiveness of a multifaceted intervention program in primary prevention of asthma in high-risk infants.
We identified 545 high-risk infants on the basis of an immediate family history of asthma. Families were randomized into intervention or control groups. Intervention measures included avoidance of house dust mite, pet allergen, and environmental tobacco smoke. Breast-feeding was encouraged with formula supplementation if necessary, and introduction of solid foods was delayed.
At 2 years of age, 19.5% of the children had asthma, and 14.7% had atopy (positive skin test response to one or more common allergens). Significantly fewer children had asthma in the intervention group compared with in the control group (16.3% vs 23.0%), with 60% less persistent asthma at 2 years. There was a 90% reduction for recurrent wheeze in the intervention group compared with that seen in the control group. Exposure to maternal environmental tobacco smoke during pregnancy or the first year was a risk factor for asthma at 2 years of age. A positive skin test response, particularly to food, at 12 months predicted asthma at 2 years. There was no significant difference for atopy between the intervention and control groups, but daycare reduced atopy at 2 years.
This multifaceted intervention program during a window of opportunity in the first year of life was effective in preventing asthma in high-risk children at 2 years of age. Future studies with this cohort at school age are important.
Avoidance of any one of the individual risk factors associated with childhood asthma has not been successful in preventing its development.
The purpose of this study is to determine the effectiveness of a multifaceted intervention program for the primary prevention of asthma in high-risk infants at 7 years of age.
Five hundred forty-five high-risk infants with an immediate family history of asthma and allergies were prospectively randomized into intervention or control groups prenatally. Intervention measures introduced before birth and during the first year of life included avoidance of house dust, pets, and environmental tobacco smoke and encouragement of breast-feeding with delayed introduction of solid foods. Assessment of outcomes at 7 years consisted of examination by pediatric allergists, methacholine inhalation tests, and allergy skin tests.
At 7 years, 469 of the 545 children were contacted, and 380 returned for further assessment. The prevalence of pediatric allergist-diagnosed asthma was significantly lower in the intervention group than in the control group (14.9% vs 23.0%; adjusted risk ratio, 0.44; 95% CI, 0.25-0.79). The prevalence of allergic rhinitis, atopic dermatitis, atopy (defined as positive skin test reactions to any common allergen), and bronchial hyperresponsiveness (defined as the provocative concentration of methacholine that induced a 20% decrease in FEV 1 from a postsaline value of less than 7.8 mg/mL) were not significantly different between the 2 groups. The prevalence of asthma (defined as wheeze without colds and the presence of bronchial hyperresponsiveness) was also significantly lower in the intervention group compared with the control group (12.9% vs 25.0%; adjusted risk ratio, 0.39; 95% CI, 0.22-0.71).
The multifaceted intervention program was effective in reducing the prevalence of asthma in high-risk children at 7 years of age.
Although guidelines for the diagnosis and management of asthma have been published over the last 15 years, there has been little focus on issues relating to asthma in childhood. Since the last revision of the 1999 Canadian asthma consensus report, important new studies, particularly in children, have highlighted the need to incorporate this new information into asthma guidelines.
To review the literature on asthma published between January 2000 and June 2003 and to evaluate the influence of new evidence on the recommendations made in the Canadian Asthma Consensus Report, 1999 and its 2001 update with a major focus on pediatric issues.
Diagnosis of asthma in young children, prevention strategies, pharmacotherapy, inhalation devices, immunotherapy and asthma education were selected for review by small expert resource groups. In June 2003, the reviews were discussed at a meeting under the auspices of the Canadian Network For Asthma Care and the Canadian Thoracic Society. Data published up to December 2004 were subsequently reviewed by the individual expert resource groups.
This report evaluates early life prevention strategies and focuses on treatment of asthma in children. Emphasis is placed on the importance of an early diagnosis and prevention therapy, the benefits of additional therapy and the essential role of asthma education.
We generally support previous recommendations and focus on new issues, particularly those relevant to children and their families. This guide for asthma management is based on the best available published data and the opinion of health care professionals including asthma experts and educators.
Cites: CMAJ. 1999 Nov 30;161(11 Suppl):S1-6110906907
Cites: Can Respir J. 2001 Mar-Apr;8 Suppl A:5A-27A11360044
Cites: Can Respir J. 2004 May-Jun;11 Suppl A:9A-18A15254605
Environmental exposures during early life have been suggested to have the greatest impact on childhood asthma. Our aim was to evaluate the risk factors associated with asthma at age 7 yr in a high-risk cohort that participated in a randomized controlled study on the primary prevention of asthma. Indoor exposures were characterized before birth and at 2 weeks, 4, 8, 12, 18, and 24 months after birth and again at 7 yr. Nasal scrapings for respiratory viruses were done at the same intervals during the first 2 yr. At age 7, the children were assessed by a pediatric allergist and had allergy skin tests. Logistic regression analysis was undertaken to evaluate the effect of exposures on asthma for the entire cohort with adjustment for group allocation. In addition to the lower risk of asthma in the intervention group, we found a higher prevalence of asthma at age 7 for males, those having a positive history of asthma in mother, father, or older siblings, for children residing in Winnipeg and for atopic subjects. Upon adjustment for intervention group assignment and baseline factors, significant environmental risk factors during year 1 included dog ownership and respiratory syncytial viral infection detected at 12 months while maternal smoking was protective. Dog ownership was a significant risk factor in year 2, but highly correlated with dog ownership in year 1. Indoor environmental exposures during year 7 were not associated with asthma at age 7. Maternal smoking at year 7 was associated with a reduced risk of asthma at 7 yr. Early-life exposures were more important determinants than those in later years. A 'window of opportunity' exists for intervention measures to be applied.
There is considerable interest in identifying children at high risk for developing atopic diseases for primary prevention. This study evaluates risk factors for detectable cord blood IgE and assesses CB-IgE in predicting asthma and other IgE-mediated allergic diseases in children at high risk because of family history. Cord blood was obtained as part of a randomized controlled trial assessing the efficacy of an intervention program in the primary prevention of IgE-mediated allergic diseases. CB-IgE was measured and the degree to which this was associated with perinatal risk factors was assessed. The cohort was then evaluated for atopic disorders at 7 yrs of age to assess the predictive value of CB-IgE. Fifty-five (19.3%) of infants had detectable CB-IgE (>/=0.5 kU/l). Maternal atopy and birth in winter months were risk factors associated with detectable CB-IgE. CB-IgE was found to be significantly associated with allergic sensitization (OR 2.22; 95% CI 1.11, 4.41) and recurrent wheeze at 7 yrs (OR 2.51, 95% CI 1.09, 5.76) but not with other outcomes. CB-IgE may be a useful measure for identifying children at high risk of atopic diseases for the purpose of primary prevention.