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The work contained within this thesis aimed to establish the Dyspnoea Challenge, a two minute graded treadmill walk test, as a measure of exertional dyspnoea in those with cardiopulmonary disease. Four experiments were conducted to develop a standardised protocol and assess the reliability, validity, and responsiveness of the Dyspnoea Challenge in two clinical populations: chronic obstructive pulmonary disease (COPD) and heart failure (HF). The work presented in this thesis serves to improve the clinical-based options for measuring exertional dyspnoea across cardiopulmonary disease. Viewed together, the results of this project show that the Dyspnoea Challenge is a reliable, valid, and responsive measure of exertional dyspnoea with three potential uses: the longitudinal measurement of symptom intensity, assessment of disease severity, and providing diagnostic data regarding underlying cardiopulmonary disease and symptom mechanisms. Although further research is required to substantiate these claims, the results within this thesis suggest the Dyspnoea Challenge has more potential than other commonly used or emerging exercise tests for measuring exertional dyspnoea in cardiopulmonary disease., Thesis (PhD Doctorate), Doctor of Philosophy (PhD), School of Health Sci & Soc Wrk, Griffith Health, Full Text

Pulmonary arterial hypertension is a rare but terminal pulmonary vascular disease characterized by elevated pressure in the pulmonary circulation coupled with right ventricular hypertrophy and failure. This disease is up to four times more common in women—a striking sex difference that cannot be explained by the contributions of sex hormones alone. This dissertation is a compilation of the first work investigating the sex biasing contributions of sex chromosomes in pulmonary arterial hypertension.In Chapter 2, we use powerful mouse models to identify the male-specific Y chromosome confers protection against the development of experimental pulmonary hypertension. In Chapter 3, we use a combination of experimental models and bioinformatic approaches to identify the gene on the Y chromosome that protects males against the development of pulmonary hypertension and its downstream effector genes. We found the Y chromosome gene Uty protects against the development of pulmonary hypertension by attenuating a proinflammatory lung response. Loss or lack of Uty gene expression results in an elevated inflammatory response that contributes detrimentally to disease severity. We identified two chemokines, Cxcl9 and Cxcl10, that are downstream of and inversely related to Uty as particularly harmful in pulmonary hypertension. We show that blocking their activity is sufficient to extend Y chromosome protection to females in a novel, preclinical therapy. In Chapter 4, we expand on our findings of downstream Uty effector genes and identify a sex-specific upregulation of Endothelin-2 that is linked to loss of Uty expression and elevated Cxcl9 and Cxcl10 levels. While the role of Endothelin-1 is known in pulmonary hypertension, the role of Endothelin-2, a proinflammatory and vasoconstrictive peptide, has not yet been studied. Our findings regarding Endothelin-2 help explain a clinical sex difference in the efficacy of endothelin receptor antagonist therapies for pulmonary hypertension whe

Pulmonary arterial hypertension is a rare but terminal pulmonary vascular disease characterized by elevated pressure in the pulmonary circulation coupled with right ventricular hypertrophy and failure. This disease is up to four times more common in women—a striking sex difference that cannot be explained by the contributions of sex hormones alone. This dissertation is a compilation of the first work investigating the sex biasing contributions of sex chromosomes in pulmonary arterial hypertension.In Chapter 2, we use powerful mouse models to identify the male-specific Y chromosome confers protection against the development of experimental pulmonary hypertension. In Chapter 3, we use a combination of experimental models and bioinformatic approaches to identify the gene on the Y chromosome that protects males against the development of pulmonary hypertension and its downstream effector genes. We found the Y chromosome gene Uty protects against the development of pulmonary hypertension by attenuating a proinflammatory lung response. Loss or lack of Uty gene expression results in an elevated inflammatory response that contributes detrimentally to disease severity. We identified two chemokines, Cxcl9 and Cxcl10, that are downstream of and inversely related to Uty as particularly harmful in pulmonary hypertension. We show that blocking their activity is sufficient to extend Y chromosome protection to females in a novel, preclinical therapy. In Chapter 4, we expand on our findings of downstream Uty effector genes and identify a sex-specific upregulation of Endothelin-2 that is linked to loss of Uty expression and elevated Cxcl9 and Cxcl10 levels. While the role of Endothelin-1 is known in pulmonary hypertension, the role of Endothelin-2, a proinflammatory and vasoconstrictive peptide, has not yet been studied. Our findings regarding Endothelin-2 help explain a clinical sex difference in the efficacy of endothelin receptor antagonist therapies for pulmonary hypertension whe

Objective: Determine the relationship between obesity and abnormal cardiopulmonary parameters in school children. Materials andMethods: The sample involved 78 children between five and 11 years of age: 47 males (60.3%) and 31 females (39.7%). All were enrolledin a specific elementary school in the city of Pachuca (Mexico). Body mass (BMI), waist circumference (WC), body fat (GC), heart rate (HR), blood pressure (BP), respiratory rate (RR) and spirometry were evaluated. A chi-square (x2) statistical test, the odds ratio and Spearman’s rank-order correlation (rs) were used. Results: In all, 23.1% of the students who were evaluated were overweight and 29.5% were obese; 38.5% and 11.5% had a HR and BP above the normal parameters, in that order; 3.8% of the population in question had a HR above average and 11.5% showed abnormal spirometric values. A relationship was found between BMI and BF and WC, BF and WC, WC and HR, BF and BP, and HR and RF. Conclusions: The prevalence of overweight and obesity found in this study was high. Children who are overweight or obese might be at increased risk of experiencing cardiopulmonary abnormalities compared to children of normal weight. It is suggested that studies on this subject be continued with a broader sample., Objetivo: determinar a relação entre obesidade e anormalidades de parâmetros cardiopulmonares em estudantes do ensino fundamental.Materiais e métodos: participaram do estudo 78 estudantes entre 5 a 11 anos de idade, 47 do gênero masculino (60,3 %) e 31 do feminino (39,7 %), pertencentes a uma escola primária particular da cidade de Pachuca (México). Avaliaram-se o índice de massa corporal (IMC), a circunferência de cintura (CC), a gordura corporal (GC), a frequência cardíaca (FC), a pressão arterial (PA), a frequência respiratória (FR) e a espirometria. Utilizaram-se os testes estatísticos qui-quadrado (x2), odds ratio e correlação de Spearman (rs). Resultados: 23,1 % dos estudantes avaliados apresentaram excesso de peso e 29,5 % obesidade. 38,5 e 11,5 % apresentaram FC e PA superiores aos parâmetros normais, respectivamente; 3,8 % da população apresentou FR acima da média e 11,5 % mostraram parâmetros espirométricos anormais. Constataram-se relações entre IMC com GC e CC, GC e CC, CC e FC, GC e PA, e FC e FR. Conclusões: as prevalências de excesso de peso e obesidade obtidas neste estudo foram altas. As crianças com excesso de peso ou obesidade poderiam ter maior risco de apresentar anormalidades cardiopulmonares em comparação às de peso normal. Sugere-se continuar com estudos sobre o tema com uma amostra mais ampla., Objetivo: determinar la relación entre obesidad y anormalidades de parámetros cardiopulmonares en escolares. Materiales y métodos:participaron 78 escolares entre 5 a 11 años de edad, 47 hombres (60,3 %) y 31 mujeres (39,7 %), pertenecientes a una escuelaprimaria particular de la ciudad de Pachuca (México). Se evaluó: índice de masa corporal (IMC), circunferencia de cintura (CC), grasacorporal (GC), frecuencia cardiaca (FC), presión arterial (PA), frecuencia respiratoria (FR) y espirometría. Se emplearon las pruebasestadísticas chi-cuadrado (x2), odds ratio y correlación de Spearman (rs). Resultados: 23,1 % de los escolares evaluados presentaronsobrepeso y 29,5 %, obesidad. El 38,5 y 11,5 % presentaron FC y PA superiores a los parámetros normales, respectivamente; 3,8 % de lapoblación presentó FR arriba del promedio y 11,5 % mostró valores espirométricos anormales. Se encontraron relaciones entre IMC conGC y CC, GC y CC, CC y FC, GC y PA, y FC y FR. Conclusiones: las prevalencias de sobrepeso y obesidad obtenidas en este estudio fueron altas. Los niños con sobrepeso u obesidad podrían tener mayor riesgo de presentar anormalidades cardiopulmonares en comparación con niños de peso normal. Se sugiere continuar con estudios en el tema en una muestra más amplia. DOI: 10.5294/aqui.2016.16.2.3