published_or_final_version / abstract / toc / Clinical Psychology / Master / Master of Social Sciences

No description available.

Rationale: Methacholine and mannitol challenges are used clinically to assess airway hyperresponsiveness (AHR). Cough during (a) high-dose methacholine challenge in individuals with methacholine-induced cough and normal airway sensitivity and (b) mannitol challenge in some individuals with asthma both occur in the absence of significant declines in forced expiratory volume in one second (FEV1). We hypothesized mechanical responses to these challenges would reflect a continuum amongst subjects with: (i) asthma; (ii) cough variant asthma (CVA) and (iii) methacholine-induced cough and normal airway sensitivity due to varying degrees of impairment/preservation of the beneficial effects of deep inspirations. Purpose: To compare cough and airway responses to mannitol and high-dose methacholine challenges between these groups. Methods: Individuals with asthma or suspected CVA were invited to participate. Subjects were challenged with mannitol and high-dose methacholine in random order 2-14 days apart. Cough frequency, spirometry and esophageal-pressure were recorded at baseline and after each dose of mannitol and methacholine to a maximal decline in FEV1 of 15% and 50% respectively. Plethysmography was used to measure lung volumes at baseline, the dose nearest to a 15% decline in FEV1 during mannitol challenge (PD15) and 20% decline in FEV1 during methacholine challenge (PC20), and at the highest dose of methacholine. Measurements were compared: (a) between groups at PD15, PC20 and the highest dose of methacholine; and (b) within groups at PD15 and PC20, and the highest equivalent level of bronchoconstriction. Results: 22 subjects (17 female; 48.0±12.7 (mean±SD years)) who completed both challenges were included. All subjects coughed during both challenges. Mechanical responses to mannitol and high-dose methacholine challenges reflected a continuum amongst groups. Six of 8 subjects with asthma were mannitol postitive (PD15=115.2±100.0 mg) and were significantly more sensitive to mannitol compared to 3 of 5 mannitol positive subjects with CVA (PD15=533.6±88.3 mg; p=0.020) and 3 of 9 mannitol positive subjects with methacholine-induced cough and normal airway sensitivity (PD15=472.8±203.0 mg; p=0.037). At the highest equivalent level of bronchoconstriction, methacholine induced significant declines in FEF50% and FEF25-75% in all subjects groups while mannitol did not. Conclusion: Mechanical responses to mannitol and high-dose methacholine challenges reflected a continuum amongst groups. / Thesis (Master, Physiology) -- Queen's University, 2012-07-27 08:58:05.298

TLRs play a key role in initiating innate immunity and in regulating the nature of the adaptive immune response. We hypothesized that functional responsiveness to TLR stimulation differs in clinically; environmentally; ethnically distinct pediatric populations. PBMC obtained from 272 children were stimulated with a panel of TLR ligands. Levels of pro- and anti-inflammatory, Th1-, Th2-associated cytokines were quantified by ELISA. We demonstrate that use of threshold concentrations of TLR4 and TLR2 ligands reveal striking differences in cytokine responses between asthmatic and non-atopic children. Specifically, non-atopic controls produce higher levels of pro-inflammatory cytokines, whereas asthmatics exhibit increased anti-inflammatory IL-10 responses. Asthmatic children exposed to environmental tobacco smoke (ETS) demonstrated elevated levels of chemokines relative to non-ETS exposed asthmatics and controls. First Nation children favor anti-inflammatory IL-10 responses, whereas Caucasian population respond to TLR activation by production of more robust pro-inflammatory and Th1 biased cytokine and chemokine responses.

The study was conducted with a total of 13980 children of the 1995 birth cohort, who were living in Manitoba by the end of December, 2006. Higher frequency of RSV-associated LRTI before 2 years was associated with higher risks of asthma diagnosis at 7 and 11 years and also with risks of transient wheeze and early persistent asthma. Higher risk of asthma diagnosis was associated with more severe episode(s) of RSV-associated LRTI within the first 2 years of life. First clinically significant RSV-LRTI between 6 and 12 months was associated with the highest risks of asthma diagnosis at 7 and at 11 years. But first RSV-associated LRTI within the first 6 months of life was associated with the highest risk of asthma/transient wheezing before the age of 3 years and early persistent asthma and transient wheeze. These associations were diminishing with increasing age of the children of the study cohort.

No description available.

New Zealand has one of the highest asthma prevalence rates among developed countries and previous research attributes this partly to poor socioeconomic conditions and to insufficient home heating in particular. Retrospective empirical studies from overseas suggest that home heating is associated with asthma rates. However, the evidence to date is not conclusive. In this thesis, I present a theoretical framework and empirically investigate the link between home heating and asthma hospital admissions in New Zealand using panel data techniques and controlling for endogeneity. The hypothesis that higher electricity prices (via less adequate heating) increase asthma admissions is tested and receives strong empirical support across a number of model specifications and datasets used.

There is evidence that children with asthma exhibit more externalizing behaviour problems than other children. Impulsive behaviours can mark the onset and severity of externalizing behaviour problems. The present paper reports an exploratory examination of relationships between functional asthma severity and impulsivity in 6 and 7 year old children with asthma (N = 16). Participants with varying functional asthma severity were recruited at age 5 from a larger community study (the Children’s Learning Study). Parents completed items from three subscales of the Connors’ Parent Rating Scale-Revised (CPRS-R), the Hyperactive-Impulsive, Conners’ Global Index: Restless-Impulsive and the DSM-IV Hyperactive-Impulsive subscales. Children completed the Two Choice Paradigm (TCP), a computer program measuring delay aversion type impulsive behaviours. Mean (SD) CPRS-R Hyperactive-Impulsive, Conners’ Global Index: Restless-Impulsive and DSM-IV Hyperactive-Impulsive subscale scores were 59 (11), 56 (10) and 59 (10) respectively. There was no correlation between functional asthma severity and delay aversion or CPRS-R subscale scores and there was no evidence of a trend for such a relationship. Preliminary investigations conducted with a small sample of 6-7 year-old children with asthma thus suggest that functional asthma severity is not related to impulsivity.

Uncontrolled oxygen is often administered to breathless patients regardless of whether hypoxaemia is present. In acute exacerbations of Chronic Obstructive Pulmonary Disease (AECOPD) this may result in carbon dioxide (CO2) retention and worsening respiratory failure in some patients. In AECOPD the main mechanism is the release of hypoxic pulmonary vasoconstriction and an increase in the physiological dead space to tidal volume ratio (VD/VT). Acute asthma and pneumonia have features in common with AECOPD, namely significant ventilation – perfusion mismatch; and there is the potential for CO2 retention to occur if uncontrolled high concentration oxygen is given. There have been no randomised controlled trials of oxygen therapy in pneumonia and only one in asthma. The potential mechanisms of any change in arterial CO2 that may occur with oxygen therapy in respiratory disorders other than COPD remain uncertain. This thesis presents work from three clinical studies. In two randomised controlled trials, high concentration oxygen was compared to titrated oxygen therapy in patients with either acute severe asthma and suspected community acquired pneumonia. Oxygen was administered for one hour in conjunction with standard medical treatment. Transcutaneous CO2 (PtCO2) was continuously monitored and the number of patients with pre-specified increases in PtCO2 were calculated. The proportion of patients with a rise in PtCO2 4 mmHg was significantly higher in the high concentration oxygen groups of both studies. In the pneumonia study 36/72 (50.0%) vs 11/75 (14.7%) met this endpoint, with a relative risk of 3.4 (95% CI 1.9 to 6.2; P <0.001), and in the asthma study 22/50 (44%) vs 10/53 (18.9%) met this endpoint, with a relative risk of 2.3 (95% CI 1.2 to 4.3; P=0.009). Similarly, a rise in PtCO2 8 mmHg was more common with high concentration oxygen. In the pneumonia study 11/72 (15.3%) vs 2/75 (2.7%) of patients met this endpoint, with a relative risk of 5.7 (95% CI 1.3 to 25.0; P=0.007), and 10/50 (20%) vs 3/53 (5.7%) of asthma patients met this endpoint, with a relative risk of 3.6 (95% CI 1.1 to 12.3; P=0.03). A third study measured the physiological response to 20 minutes of 100% oxygen in chronic severe asthma, with comparison to a group of negative controls (normal subjects) and positive controls (COPD patients). There was a significant rise in PtCO2 of similar magnitude in the asthma and COPD groups compared with the normal controls. The mechanism of the PtCO2 rise was similar in asthma and COPD, with an increase in VD/VT but no change in minute ventilation. These studies demonstrate than uncontrolled high concentration oxygen has the potential to cause CO2 retention in respiratory diseases other than COPD, and that in asthma the mechanism of hypercapnia is similar to that in AECOPD. In acute asthma and community-acquired pneumonia oxygen should be administered only to those patients with evidence of arterial hypoxaemia in a dose that relieves hypoxaemia without causing hyperoxia, thereby achieving the benefits of oxygen therapy while reducing the potential for harm.

No description available.