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No description available.

A thirty year follow-up survey was carried out to determine the prevalence of adult onset wheeze in a randomly selected community cohort of 2,056 adults who had had no childhood respiratory symptoms when they were originally studied in 1964. New onset wheezing symptoms developed at a steady rate of 0.5 per 100 person years between age 15 and 14; 11.5% of subjects reported having had an attack of wheezing for the first time during this period of their lives. Adult onset disease accounted for a greater proportion (62.9%) of current wheezing in middle age than child onset disease (37.1%). The risk of adult onset wheeze among all cases who had ever wheezed since age 15 increased with low socioeconomic status, current smoking, positive atopic status and positive family history of atopic disease. Gender was not related to risk of wheeze. Vitamin C and E consumption were inversely related to the risk of current wheeze (i.e. wheeze in the previous 12 months); analyses stratified by social class and smoking habit suggested that these inverse associations were stronger in the manual compared to the nonmanual class, and among smokers compared to nonsmokers. Childhood factors, including father's social class, sibship structure and common childhood infections were not related to adult onset wheeze. The pattern of significant independent risk factors differed between three distinct subgroups of cases who reported doctor-diagnosed asthma (n=24), chronic cough and phlegm (n=31) or other wheeze (n=47). Manual social class was associated with cough and phlegm and other wheeze. Smoking was only related to cough and phlegm. Atopy was associated with doctor-diagnosed asthma and with cough and phlegm. Family history of atopic disease was related to all subgroups, suggesting that despite apparent heterogeneity in diagnostic labelling, concurrent symptoms and other risk factors, the different forms of adult onset wheeze may share a common allergic basis.

Background and Rationale: Asthma and overweight are public health concerns. Lifestyle, including dietary and activity patterns, is associated with overweight and asthma. Moreover, an association between these two diseases has been described. Yet, few studies have considered these associations longitudinally in youth. Methods: Based on data from the 1995 Manitoba Birth Prospective Cohort (n=723, 404 [55.9%] boys), we designed a series of studies to address the question: “Do obesity and related lifestyle behaviours influence asthma and airway hyperresponsivess (AHR) outcomes in children?” Following protocol for a mixed methods sequential explanatory design study, we first considered this research question using quantitative methods. Exposure variables included weight status (body mass index (BMI); BMI z-scores; normal weight vs. overweight), diet, physical activity and screen time. Outcome variables included asthma and AHR at 8-10 years old and at 12-13 years old. Quantitative findings provided direction for the qualitative investigations. That is, we sought to further explain some of the quantitative findings using qualitative methods. For the qualitative portion of this dissertation, 15-16 year old youth were purposively selected (Winnipeg residency, asthma status, gender) from the 1995 Manitoba Prospective Birth Cohort. Due to recruitment challenges, participation was supplemented with youth from the Canadian Asthma Primary Prevention Study, using the same purposive selection criteria. Quantitative Results: Overweight at 12-13 years old was associated with a two-fold increased odds of persistent asthma in girls. In contrast, boys within the highest BMI quartile at 8-10 years old were nearly twice as likely to have remittent asthma at 12-13 years old. High vegetable intake was protective against allergic asthma and moderate-to-severe AHR by 50% and 42%, respectively. High screen time at 8-10 years old, particularly amongst overweight youth, was associated with an increased odds of asthma, but not AHR at 8-10 years and 12-13 years; there were no associations between physical activity, asthma and AHR. Qualitative Results: Youth spoke of asthma as a condition that neither limits physical activity, nor is an excuse for refraining from physical activity. Conclusions: Modest evidence that some quantitatively-measured weight and related lifestyle behaviours during the pubertal years is associated with asthma. Yet, qualitative data suggest that youth with asthma believe that physical activity is achievable despite their condition, although some describe that asthma interferes with physical activity.

Background and Rationale: Asthma and overweight are public health concerns. Lifestyle, including dietary and activity patterns, is associated with overweight and asthma. Moreover, an association between these two diseases has been described. Yet, few studies have considered these associations longitudinally in youth. Methods: Based on data from the 1995 Manitoba Birth Prospective Cohort (n=723, 404 [55.9%] boys), we designed a series of studies to address the question: “Do obesity and related lifestyle behaviours influence asthma and airway hyperresponsivess (AHR) outcomes in children?” Following protocol for a mixed methods sequential explanatory design study, we first considered this research question using quantitative methods. Exposure variables included weight status (body mass index (BMI); BMI z-scores; normal weight vs. overweight), diet, physical activity and screen time. Outcome variables included asthma and AHR at 8-10 years old and at 12-13 years old. Quantitative findings provided direction for the qualitative investigations. That is, we sought to further explain some of the quantitative findings using qualitative methods. For the qualitative portion of this dissertation, 15-16 year old youth were purposively selected (Winnipeg residency, asthma status, gender) from the 1995 Manitoba Prospective Birth Cohort. Due to recruitment challenges, participation was supplemented with youth from the Canadian Asthma Primary Prevention Study, using the same purposive selection criteria. Quantitative Results: Overweight at 12-13 years old was associated with a two-fold increased odds of persistent asthma in girls. In contrast, boys within the highest BMI quartile at 8-10 years old were nearly twice as likely to have remittent asthma at 12-13 years old. High vegetable intake was protective against allergic asthma and moderate-to-severe AHR by 50% and 42%, respectively. High screen time at 8-10 years old, particularly amongst overweight youth, was associated with an increased odds of asthma, but not AHR at 8-10 years and 12-13 years; there were no associations between physical activity, asthma and AHR. Qualitative Results: Youth spoke of asthma as a condition that neither limits physical activity, nor is an excuse for refraining from physical activity. Conclusions: Modest evidence that some quantitatively-measured weight and related lifestyle behaviours during the pubertal years is associated with asthma. Yet, qualitative data suggest that youth with asthma believe that physical activity is achievable despite their condition, although some describe that asthma interferes with physical activity.

Airway hyperresponsiveness (AHR) is a cardinal feature of asthma that is aggravated by environmental air pollution (EAP). Splenocyte tyrosine kinase Syk has been associated with asthma pathogenesis. Therefore, we sought to investigate the effect of Syk inhibition on AHR and its exacerbation by EAP. For this purpose, we examined Syk protein expression in lung homogenates from three murine models of ovalbumin (OVA)-induced asthma expressing different pathophysiological features of the disease: airway inflammation, AHR and remodeling. Increased Syk expression was observed only in the chronic model of airway inflammation and remodeling. In vivo Syk inhibition attenuates AHR in this model, and further augmentation induced by EAP without affecting the underlying airway inflammation. We demonstrated, for the first time, that Syk inhibition effectively reverted AHR in an already established chronic model of asthma. These findings highlight the therapeutic potential of targeting Syk for the treatment of asthma and its exacerbations by EAP.

Airway hyperresponsiveness (AHR) is a cardinal feature of asthma that is aggravated by environmental air pollution (EAP). Splenocyte tyrosine kinase Syk has been associated with asthma pathogenesis. Therefore, we sought to investigate the effect of Syk inhibition on AHR and its exacerbation by EAP. For this purpose, we examined Syk protein expression in lung homogenates from three murine models of ovalbumin (OVA)-induced asthma expressing different pathophysiological features of the disease: airway inflammation, AHR and remodeling. Increased Syk expression was observed only in the chronic model of airway inflammation and remodeling. In vivo Syk inhibition attenuates AHR in this model, and further augmentation induced by EAP without affecting the underlying airway inflammation. We demonstrated, for the first time, that Syk inhibition effectively reverted AHR in an already established chronic model of asthma. These findings highlight the therapeutic potential of targeting Syk for the treatment of asthma and its exacerbations by EAP.

Allergic asthma is a syndrome characterized by respiratory distress in response to environmental triggers. This atypical response to an allergen is an over reaction of the immune system causing an influx of inflammatory cells into the airway and concomitant airway smooth muscle constriction. Firstly, we demonstrate using whole house dust mite (HDM) extract as a sensitizing allergen produces an equivalent or more robust hyperresponsive and inflammatory reaction than can be achieved with the widely used ovalbumin (OVA) sensitization / challenge protocol. Secondly, we investigated the role of caveolin-1 in the pathophysiology of allergic asthma . Our data suggest an important role for cav-1 in down regulating allergic airway inflammation, leading to reduced airways hyperresponsiveness and mucus overproduction.

Allergic asthma is a syndrome characterized by respiratory distress in response to environmental triggers. This atypical response to an allergen is an over reaction of the immune system causing an influx of inflammatory cells into the airway and concomitant airway smooth muscle constriction. Firstly, we demonstrate using whole house dust mite (HDM) extract as a sensitizing allergen produces an equivalent or more robust hyperresponsive and inflammatory reaction than can be achieved with the widely used ovalbumin (OVA) sensitization / challenge protocol. Secondly, we investigated the role of caveolin-1 in the pathophysiology of allergic asthma . Our data suggest an important role for cav-1 in down regulating allergic airway inflammation, leading to reduced airways hyperresponsiveness and mucus overproduction.

BACKGROUND:Airway hyperresponsiveness (AHR), a primary characteristic of asthma, involves increased airway smooth muscle contractility in response to certain exposures. We sought to determine whether common genetic variants were associated with AHR severity.METHODS:A genome-wide association study (GWAS) of AHR, quantified as the natural log of the dosage of methacholine causing a 20% drop in FEV1, was performed with 994 non-Hispanic white asthmatic subjects from three drug clinical trials: CAMP, CARE, and ACRN. Genotyping was performed on Affymetrix 6.0 arrays, and imputed data based on HapMap Phase 2, was used to measure the association of SNPs with AHR using a linear regression model. Replication of primary findings was attempted in 650 white subjects from DAG, and 3,354 white subjects from LHS. Evidence that the top SNPs were eQTL of their respective genes was sought using expression data available for 419 white CAMP subjects.RESULTS:The top primary GWAS associations were in rs848788 (P-value 7.2E-07) and rs6731443 (P-value 2.5E-06), located within the ITGB5 and AGFG1 genes, respectively. The AGFG1 result replicated at a nominally significant level in one independent population (LHS P-value 0.012), and the SNP had a nominally significant unadjusted P-value (0.0067) for being an eQTL of AGFG1.CONCLUSIONS:Based on current knowledge of ITGB5 and AGFG1, our results suggest that variants within these genes may be involved in modulating AHR. Future functional studies are required to confirm that our associations represent true biologically significant findings.